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Inhalt
Oncol Res Treat 2022;45(suppl 1):5
DOI: 10.1159/000521004
Inhalt
Best-of-Abstract-Vortrag
Breast Cancer 18
Cancer Prevention 40
Developmental Therapeutics: Immunotherapy/Cellular 49
Epidemiology 57
Gastrointestinal (Colorectal) Cancer 62
Gastrointestinal (Non-colorectal) Cancer 77
Genitourinary Cancer including Prostate Cancer 95
Gynecologic Cancer 112
Head and Neck Cancer 124
Health Economy/Public Health 133
Leukemia, Myelodysplasia, and Transplantation 140
Lung Cancer 144
Lymphoma and Plasma Cell Disorders 164
Oncological Pharmacy 183
Paediatric Cancer 193
Palliative Care 197
Psychooncology 201
Quality-of-Life 213
Radiation 220
Rehabilitation and long-term burden in social medicine (survivor) 225
Sarcoma 229
Supportive Care 237
Surgical Oncology 252
Poster
Articial intelligence in oncology 7
Biomarker 11
Breast Cancer 18
Cancer of Unknown Primary (CUP) 39
Cancer Prevention 40
Central Nervous System Tumors 44
Developmental Therapeutics: Immunotherapy/Cellular 49
Endocrine Tumors (e. g. thyroid cancer, adrenal tumor, neuroendocrine tumor) 55
Epidemiology 57
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© 2022 S. Karger AG, Basel
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Inhalt
Oncol Res Treat 2022;45(suppl 1):6
DOI: 10.1159/000521004
Gastrointestinal (Colorectal) Cancer 62
Gastrointestinal (Non-colorectal) Cancer 77
Genitourinary Cancer including Prostate Cancer 95
Geriatric Oncology 110
Gynecologic Cancer 112
Head and Neck Cancer 124
Health Economy/Public Health 133
Imaging 138
Leukemia, Myelodysplasia, and Transplantation 140
Lung Cancer 144
Lymphoma and Plasma Cell Disorders 164
MIC/Robotic 174
Molecular Pathology 174
Molecular Therapeutics 176
Novel Agents/Early Clinical Trials 178
Novel developments: Cytotoxic Chemotherapy 179
Nursing in Oncology 180
Oncological Pharmacy 183
Other Topics 184
Paediatric Cancer 193
Palliative Care 197
Psychooncology 201
Quality-of-Life 213
Radiation 220
Rehabilitation and long-term burden in social medicine (survivor) 225
Sarcoma 229
Skin Cancer including Melanoma 235
Supportive Care 237
Surgical Oncology 252
Translational Oncology 254
Autorenindex 264
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Abstracts
Oncol Res Treat 2022;45(suppl 1):7–284
DOI: 10.1159/000521004
© 2022 S. Karger AG; Basel
Articial intelligence in oncology
Poster
174
Using a RNN-based Dependency Grammar to associate
structured data from histological reports with tissue samples
Julian Dörenberg1; Nadine Gaisa2; Jan Bednarsch3; Lara Heij2,3;
EdgarDahl1,2
1RWTH cBMB Biobank im Institut für Pathologie, Medizinische Fakultät RWTH
Aachen University, Aachen, Deutschland
2Institut für Pathologie, Universitätsklinikum Aachen, Aachen, Deutschland
3Klinik für Allgemein-, Viszeral- und Transplantationschirurgie,
Universitätsklinikum Aachen, Aachen, Deutschland
Background: Availability of structured data is becoming an increasingly
important factor for AI-based analyses of large sets of cancer data. Still,
pathologists in Germany oen record their histological ndings in pathol-
ogy reports using oating text. To aggregate these important tumor-as-
sociated data with further clinical data and cancer samples present in
biobanks, it is critical to convert these report into a structured form. is
can be done by using a Dependency Grammar (DG)1. A recurrent neural
network (RNN) based DG parser is provided by the framework supar2.
Methods: A DG parser trained on non-medical data is used to nd gram-
matical relations between words1. e relations are ltered for requested
data by using UMLS3 and regular expressions.
Result: On 165 sentences randomly selected from breast cancer pathology
reports, the parser correctly generated 97% of the binary relations which
contain medical terms. On a dierent set of 20 reports on hepatocellular
carcinoma the tool successfully extracted 98% of the requested data.
Discussion: e approach passed a proof-of-concept. Although the train-
ing data do not contain medical terms, the parsing accuracy is high on
histological reports. So far, the performance is not aected by the entity
being diagnosed and dierent vocabularies.
Conclusion: DGs can be used to extract data from standard German
pathology reports. As the evaluation corpus so far is very small, it has to be
extended. Aer further evaluation, the tool will eventually provide arbi-
trary information from pathology reports for usage in medical research.
Indication of source:
1. Dozat et. al. Deep Biane Attention for Neural Dependency Parsing. Confer-
ence paper at ICLR, 2017
2. Yan Zhangs. Supar. https://github.com/yzhangcs/parser, 2017
3. Bodenreider. e Unied Medical Language System (UMLS): integrating bio-
medical terminology. In: Nucleic Acids Research, 2004
Disclosure Statement: e authors declare no conict of interest.
594
Automatic extraction of data from medical documents
Georg Emons1; Marcel Markus1; Markus Mandrella1; Maike Greve2;
LutzKolbe2; Michael Ghadimi1; Jens Jakob1
1Klinik für Allgemein-, Viszeral- und Kinderchirurgie, Universitätsmedizin
Göttingen, Deutschland
2Digital Health Research Group (DHRG), Georg-August-Universität Göttingen,
Lehrstuhl für Informationsmanagement, Göttingen, Deutschland
Background: Medical documents are part of daily clinical and research
routine, containing elementary patient data essential for critical tasks
such as estimating prognosis or deciding on individualized tumor therapy.
However, as there is no standardized format for medical documents data
extraction is mostly done by hand. is laborious and numb task is prone
to error, resulting in inconsistent research data or improper treatment
decisions. e aim of this study was to develop and test the reliability of a
digital algorithm extracting the TNM status from pathology-reports.
Methods: Pathology-reports of 600 colorectal cancer patients treated at
the Universitätsmedizin Göttingen (UMG) were obtained in Portable
Document Format (PDF). Using text mining soware we generated an
algorithm to detect, extract and export the Classication of Malignant
Tumors (TNM) status of each patients tumor. Results were then com-
pared to manually extracted data from the “Oncostar” database which
is used at the UMG to present data for multidisciplinary tumor boards
and data transfer into the Krebsregister. If conicting data was found, the
original pathology-report was consulted to determine the incorrect data
transfer.
Result: e correctness in the Onkostar-database was as follows T: 92,3%,
N: 98,4%, M: 98,4%, L: 100%, V: 99,5%, R: 99,5%. e correctness of the
automated data extraction algorithm was as follows T: 97,53%, N: 98, 36%,
M: 98,36%, L: 99,59%, V: 100%, R: 98,36%. ere was no statistically dif-
ference between manual and automated data transfer.
Discussion: Despite advances in digital patient data management, up to
this date, there is no standardized, machine readable format for the patho-
logical report used in daily clinical routine. Here we present an algorithm
based on machine learning, automatically extracting TNM-Information
from unstructured reports.
Conclusion: is pilot study demonstrates that automated extraction of
TNM status from pathology reports is feasible and reliable.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts8
689
Identication and classication of tumor cells in Barrett’s
carcinoma patients by Hyperspectral imaging (HSI)
Marianne Maktabi1; Claire Chalopin1; Yannis Wichmann2;
RicardoSchmidt2; Katrin Schierle3; Hannes Köhler1; Ines Gockel2;
RenéThieme2
1Universität Leipzig, Innovation Center Computer Assisted Surgery (ICCAS),
Leipzig, Deutschland
2Univesitätsklinikum Leipzig, Klinik und Poliklinik für Viszeral-, Transplantations-,
Thorax- und Gefäßchirurgie, Leipzig, Deutschland
3Univesitätsklinikum Leipzig, Institut für Pathologie, Leipzig, Deutschland
Background: Discrimination of malignant and non-malignant cells of
histopathologic specimens is a key step in cancer diagnosis. Hyperspectral
imaging (HSI), as recently applied in medicine, as a novel technology
combining imaging with spectroscopy. HSI allows the determination of a
spectrum e.g. between the visual and near-infrared light and it might by
the usage used to identify and classify cancer cells by machine learning
algorithms. Machine learning algorithms are powerful tools for cancer cell
identication and classication using HSI data.
Methods: Aer surgical resection, specimens of Barretts carcinoma
(N=96)) and colorectal cancer (N=36) were xed in 4% formaldehyde,
slices were conducted (3µm) and stained with hematoxylin and eosin
(HE). Standard machine learning algorithm for classication were applied.
Result: We were able to analyze esophageal adenocarcinoma (EAC),
tumor stroma and squamous epithelium cells by HSI. Dierences in the
absorbance of squamous epithelium and EAC cells were determined at
eosins and hematoxylins maximal absorption (530 nm and 590 nm). e
intragroup variances for the squamous epithelium and the esophageal
adenocarcinoma cells were quite low. An accuracy of 71% for EAC and
stroma cells, and 73% for squamous epithelium was achieved by using an
MLP. Furthermore, we distinguish between cancer and healthy tissue in
histopathological slides of colorectal specimens. We achieved a high sen-
sitivity and specicity of 80% and 82%, respectively by using a recurrent
neuronal network combined with a convolutional neuronal network with
a learning rate of 0.001.
Discussion: GI cancer cells show specic spectral alterations due to their
HE-staining, when measured by HSI. However, the training algorithms
need a further validation to foster a semi-automatic decision-making pro-
cess in histopathological tumor cell identication.
Conclusion: However, the histopathological tumor cell identication
needs further validation of the training algorithms to foster a semi-auto-
matic decision-making process.
Disclosure Statement: e authors declare no conict of interest.
870
Prospective, Multi-Center, Articial Intelligence Study for
Early Prediction of Serious Events under Treatment Is Now
Open for Recruitment in Breast Cancer - OMCAT Trial in
Progress
Christian Horst Tonk1,2; Ronald E. Kates2; Sherko Kümmel3;
FatimaCardoso4; Timo Schinköthe2,5; Nadia Harbeck5; Peter Staib6;
AnnetteSchmidt1,7
1Institut für Sportwissenschaft, Universität der Bundeswehr München,
Sportbiologie, Neubiberg, Deutschland
2CANKADO GmbH, Ottobrunn, Deutschland
3Interdisziplinäres Brustkrebszentrum, Kliniken Essen-Mitte, Evang.
Huyssens-Stiftung Essen-Huttrop, Essen, Deutschland
4Breast Unit, Champalimaud Clinical Centre/Champalimaud Foundation, Lisboa,
Portugal
5Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, LMU Klinikum,
Brustzentrum und CCC München, München, Deutschland
6Sankt Antonius Hospital Eschweiler, Eschweiler, Deutschland
7Forschungszentrum Digitalisierung des Gesundheitswesens, Universität der
Bundeswehr München, Neubiberg, Deutschland
Background: Aim of the OMCAT trial (‘One Million CAncer Treatment
months, NCT04531995) is improvement of cancer patient care and
safety by developing articial intelligence (AI)-based, incident predic-
tion algorithms. Incident detection allows early notication of treatment
teams, enabling timely management changes or interventions. Ultimately
the algorithms can also support improved health resource allocation.
OMCAT aims to provide learning databases in breast cancer comprising
both electronic patient reported outcome (ePRO) data using the mobile
medical device ‘CANKADO PRO-React’ and ground truth outcome data,
which provide disease-specic events of interest (“incidents”) veried by
the physician (e.g., during patient examinations).
Method: Incident prediction is posed as an application of stochastic time
series analysis using AI and knowledge engineering technology. e learn-
ing process begins by tting individualized and disease-specic stochastic
process models to “incident-free” intervals extracted from the ePRO data
series. Incidents produce detectable deviations from “ordinary” ePRO
uctuations. e algorithms are trained on CANKADO PRO-React data
to produce real-time risk functions for predicting incidents on a clinically
specied time horizon.
Result: Considering heterogeneity and combinatorics of diseases, stages,
therapies, and types of events considered in this study, the AI algorithms
aim to discover about 360 distinct predictive relationships. e estimate
of one million treatment months is derived from statistical power analysis
of this target, considering estimated median documentation time of six
months per patient and estimated 400-500 patients per predictive rela-
tionship. To date, 53 centers in Germany have expressed interest in partic-
ipating. is participation level will enable proof of principle.
Conclusions: OMCAT opens a whole new path towards evidence-trained
AI and a novel combination of patient observation and predictive care.
e goals of OMCAT are ambitious and will therefore require many more
supporters.
Disclosure Statement: e authors declare the following: M.Sc. Christian Tonk
hat ein Anstellungsverhältnis mit der CANKADO GmbH, Dr. Ronald E. Kates hat
ein Angestelltenverhältnis mit der CANKADO GmbH, Prof. Dr. Timo Schinköthe
ist Geschäsführer und Gesellschaer der CANKADO GmbH
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 9
877
Automated QTc Diagnostics for Oncological Routine Via
an AI-based Smartphone APP by Using a Single-Lead ECG
Christian Horst Tonk1,2; Timo Schinköthe2,3; Nadia Harbeck3;
VandaCarmelo4; Joana Gomes Feliciano5; Rachel Würstlein3;
SherkoKümmel6; Annette Schmidt1,7
1Institut für Sportwissenschaft, Universität der Bundeswehr München,
Sportbiologie, Neubiberg, Deutschland
2CANKADO GmbH, Ottobrunn, Deutschland
3Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, LMU Klinikum,
Brustzentrum und CCC München, München, Deutschland
4Hospital da Luz, Lisboa, Portugal
5Hospital Cruz Vermelha, Lisboa, Portugal
6Interdisziplinäres Brustkrebszentrum, Kliniken Essen-Mitte, Evang. Huyssens-
Stiftung Essen-Huttrop, Essen, Deutschland
7Forschungszentrum Digitalisierung des Gesundheitswesens, Universität der
Bundeswehr München, Neubiberg, Deutschland
Background: Long QT syndrome is a common cardiotoxic side eect of
various anti-tumor drugs. Previous cardiological monitoring of oncolog-
ical patients is primarily complex and requires for non-internal oncol-
ogists a consultation. erefore, the QTc-Tracker smartphone APP was
developed to allow an automatic determination of the QT time using the
smartphone APP. However, since single-lead ECG devices are signi-
cantly more susceptible to interference, the determination of the QT time
is more complex than with 12-lead ECGs.
Methods: Self-tracker single-lead ECG devices were used to record the
lead I signal. e ECG recordings were analyzed in the APP and passed
on to an external cardiologist as reference. e APP used articial intelli-
gence and was trained in the rst phase and validated in the second phase.
e rst phase aimed to improve QT time detection. e results of the
APP were compared with the ndings of the external cardiologist. In both
phases, ECGs from breast cancer patients receiving ribociclib were used.
Result: A total of 1889 single-lead ECGs were carried out. 248 of these
could not be evaluated (13%). QTc prolongation, according to CTCAE,
was diagnosed in 41 cases (2.5%). 878 of the evaluable ECGs were used
for the training phase and 763 for the evaluation phase. In the rst group
(before the improvement), the sensitivity to automatically detect a pro-
longation of the QT time was 36%, and the specicity was 96%. In the
evaluation collective (aer the training), the sensitivity went up to 85%,
and the specicity was unchanged at 96%.
Conclusion: e trained method of the QTc tracker is able to reliably
detect a QT time lengthening even without a cardiological diagnosis only
by using single-lead self-tracker ECG’s. In the rare cases in which an elon-
gation was not detected, the cardiac diagnosis was only a few milliseconds
above the threshold value. is articial intelligence-based smartphone
APP is not intended to replace the cardiological diagnosis, but it can sim-
plify routine processes and help to decide which patients need a cardio-
logical examination more urgently.
Disclosure Statement: e authors declare the following: M.Sc. Christian
Tonk hat ein Anstellungsverhältnis mit der CANKADO GmbH, Prof. Dr. Timo
Schinköthe ist Geschäsführer und Gesellschaer der CANKADO GmbH
899
Using AI to Process Longitudinal Data - a Proof of Concept
Benedikt Sprecher1; Ronald E. Kates2; Christian Horst Tonk2,3;
Timo Schinköthe2,4; Annette Schmidt3,5
1Fakultät für Informatik - Institut für technische Informatik, Universität der
Bundeswehr München, Neubiberg, Deutschland
2CANKADO GmbH, Ottobrunn, Deutschland
3Institut für Sportwissenschaft, Universität der Bundeswehr München,
Sportbiologie, Neubiberg, Deutschland
4Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, LMU Klinikum,
Brustzentrum und CCC München, München, Deutschland
5Forschungszentrum Digitalisierung des Gesundheitswesens, Universität der
Bundeswehr München, Neubiberg, Deutschland
Background: In various elds outside of medicine, AI-supported systems
have been established that can predict an undesirable event. e purpose
of such systems is to detect events earlier and, if necessary, to be able to
prevent them. In medicine, it would be particularly interesting to be able
to make such predictions based solely on patient observations.
Methods: e usage from 323 patients with advanced breast cancer with
a total of 78542 documentation days was used. In addition, the premature
termination of use was dened as an undesirable event. e data was then
processed and annotated. A deep-learning neural network (NN) classi-
er was trained on this dataset independently on all documented days to
predict this target endpoint. e patient classier score was computed by
averaging over daily scores. Overall classier accuracy and binary cross
entropy loss were computed as performance indicators on training and
test data sets (2:1 split).
Result: Aer tuning the hyperparameters, the best-performing NN
comprised three hidden layers, each with 88 neurons, using ReLU (lin-
ear ramp) activation, and an output layer using sigmoid activation. is
model achieved 98% accuracy on training data with binary cross entropy
loss of 0.5 and 89% accuracy with a similar loss of 0.49 on the test set.
Discussion: An extension of these results will be to model individual
longitudinal data by time series analysis, taking cumulative eects into
account, and to quantify the predictive horizon as an additional key per-
formance indicator for applications.
Conclusion: ese rst results demonstrate that longitudinal medical data,
particularly ePRO data, have predictive value for a clinical target endpoint
and can be modeled using machine learning algorithms. Performance will
generally depend on medical context, available input data, specication of
clinical target endpoints, and statistical and AI modeling details.
Disclosure Statement: e authors declare the following: M.Sc. Christian Tonk
hat ein Anstellungsverhältnis mit der CANKADO GmbH, Dr. Ronald E. Kates hat
ein Anstellungsverhältnis mit der CANKADO GmbH, Prof. Dr. Timo Schinköthe
ist Geschäsführer und Gesellschaer der CANKADO GmbH
980
Validation and Implementation of a Decision Support System
for Quality Assurance of Tumor Boards - Experiences from a
Certied Prostate Cancer Center
Dina Sahi1; David Hoier2; Petra Stamm3; Carolin Groß-Opho-Müller2;
Michael Hallek2; Axel Heidenreich4
1Heilig Geist-Krankenhaus Cologne, Department of Urology, Köln, Deutschland
2University of Cologne, Faculty of Medicine and University Hospital Cologne,
Department I of Internal Medicine, Department I of Internal Medicine, Center for
Integrated Oncology Aachen Bonn Cologne Duesseldorf, Köln, Deutschland
3Heilig Geist-Krankenhaus Cologne, Department of Urology, Köln, Deutschland
4University of Cologne, Faculty of Medicine and University Hospital Cologne,
Department of Urology, Uro-Oncology and robot assisted surgery, Köln,
Deutschland
Background: Certied Cancer Centers must present all patients in mul-
tidisciplinary tumor boards (MTD), including standard cases with well-
established treatment strategies. Too many standard cases can absorb
much of the available time, which can be unfavorable for the discussion
of complex cases. In any case, this leads to a high quantity, but not neces-
sarily a high quality of tumor boards. Our aim was to develop a partially
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts10
algorithm-driven decision support system (DSS) for smart devices to
provide evidence-based recommendations for standard cases of rst-line
therapy of common solid tumors. To assure quality, we compared each
single digital decision with recommendations of experienced MTD and
obtained the concordance rates using the example of prostate cancer.
Methods: 276 prostate cancer patients presented in the MTD of the uro-
logical department of the Heilig Geist-Krankenhaus Cologne from 2018
to 2020 have been evaluated. e questions addressed to MTD were again
answered using DSS. All blinded pairs of answers were assessed for dis-
crepancies by independent reviewers.
Results: Overall concordance rate was 94% (260/276). Stage specic con-
cordance rates were 90% (stage I), 100% (stage II), 87.7% (stage III), and
99.5% (stage IV). Aer independent expert review for cases that were ini-
tially considered non-concordant, the concordance rate could be remark-
ably increased to 100%, 100%, 98.5% and 98.2%.
Discussion: e reliability of any DSS is the key feature before implemen-
tation in clinical routine. Although our DSS seems to be a reliable tool,
continuous adjustment with clinical reality and cross-validation with dif-
ferent hospitals are a necessary requirement to keep up with the dynamic
evolution of therapeutic options.
Conclusion: e quality of therapeutic decisions provided in tumor
boards is perhaps the most relevant criterion for optimal cancer outcome.
is DSS aims to provide optimal recommendations for standard cases,
to relieve tumor boards in favor of complex cases and also to objectively
present the quality of oncology care.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
1031
Automated prostate cancer identication facilitates
prognosismarker assessment in11’845 prostate
cancersusing articial intelligence and BLEACH&STAIN
multiplex uorescence immunohistochemistry
Niclas C. Blessin1; Jan H. Müller1; Tim Mandelkow1; Elena Bady1;
Magalie C. J. Lurati1; Claudia Hube-Magg1; Markus Graefen2;
Guido Sauter1; Sarah Minner1; Stefan Steurer1
1Uniklinikum Hamburg-Eppendorf, Pathologie, Hamburg, Deutschland
2Martiniklinik am UKE GmbH, Urologie, Hamburg, Deutschland
Background: Although most prostate cancers behave in an indolent
manner, a small proportion is highly aggressive. To evaluate the patients
risk,several prognosis parameters, that can be accompanied by a high
interobserver variability has been established. A reproducible prognostic
evaluation is lacking.
Methods: To enable automated prognosis marker quantication, wehave
developed and validated a framework for automated prostate cancer
detection that comprises three dierent articial intelligence analysis
steps and an algorithm for cell-distance analysis of BLEACH&STAIN
immunohistochemistry. We have used the analysis framework to measure
PSA, PSMA, INSM1, AR, Ki-67, CD56, Chromogranin A, Synaptophysin,
CD8 in a cohort of 11’845 prostate cancers.
Result: e Ki-67 labeling index provided the strongest prognostic
information among all analyzed prognosis marker in 11’845 successfully
analyzed prostate cancers (p<0.001 each). e combined analysis of the
Ki-67-LI and Gleason grades obtained on identical tissue spots showed
that the Ki-67-LI added signicant additional prognostic information
in case of classical ISUP grades (AUC:0.82 [p=0.002]) and quantitative
Gleason grades (AUC:0.83 [p=0.018]). Several combinations of these
8 prognosis markers were combined to prognosis scores and used for
unsupervised clustering to identify a proportion of prostate cancers with
a particularly poor prognosis (p<0.001 each).
Conclusion: Automated prostate cancer identication enables fully auto-
mated prognosis marker assessment in routine clinical practice using
deep learning and BLEACH&STAIN mfIHC.
Disclosure Statement: e authors declare the following: e AR (MSVA-367R),
the INSM1 (MSVA-456R), the Ki-67 (MKI-67/6517R), the Chromogranin A (MS-
VA-380R) and the Synaptophysin antibody clone MSVA-462R were provided from
MS Validated Antibodies GmbH (owned by a family member of GS).
1054
BLEACH&STAIN, a novel multiplex uorescence
immunohistochemistry framework that facilitates a fast
high-throughput analysis of >15 biomarkers in more than
3000 human carcinomas
Elena Bady1; Katharina Möller1; Nicolaus F. Debatin1; Tim Mandelkow1;
Claudia Hube-Magg1
1Universitätsklinikum Hamburg-Eppendorf, Pathologie, Hamburg, Deutschland
Background: Multiplex uorescence immunohistochemistry (mfIHC)
approaches were yet either limited to 6 markers or limited to a small
(1.5cmx1.5cm) tissue size that hampers translational studies on large tis-
sue microarray (TMA) cohorts.
Methods: To assess more markers in a large patient cohort, we have
developed a BLEACH&STAIN mfIHC approach that enables the anal-
ysis of≥15 biomarkers in 3098 tumor samples from 44 dierent carci-
noma entities within one week and without costly instrumentalization.
An articial intelligence-based framework – incorporating three dierent
deep learning systems – for automated marker quantifcation was used to
interoperate the BLEACH&STAIN data.
Result: is approach was used to study the relationship between PD-L1
expression on multiple dierent cell types and the relationship with var-
ious leucocyte subtypes (PD-L1, PD-1, CTLA-4, panCK, CD68, CD163,
CD11c, iNOS, CD3, CD8, CD4, FOXP3, CD20, Ki67, CD31). Comparing
the automated and deep learning-based BLEACH&STAIN PD-L1 anal-
ysis framework with conventional brighteld PD-L1 data revealed a
high concordance in tumor cells (p<0.0001) as well as immune cells
(p<0.0001) and an accuracy of our approach ranging from 90% to 95.2%.
Unsupervised clustering showed that a major proportion of the three
PD-L1 phenotypes (i.e., PD-L1+ tumor and immune cells [G1], PD-L1+
immune cells [G2], PD-L1 negative [G3]) were either inamed (G1.1,
G2.1, G3.1) or non-inamed (G1.2, G2.2, G3.2) and showed distinct spa-
tial orchestration patterns.
Conclusion: BLEACH&STAIN mfIHC in combination with a deep learn-
ing-based framework for automated PD-L1 assessment on tumor and
immune cells enabled a rapid and comprehensive assessment of 15 bio-
markers across more than 3000 tumor entities that is quick and easy to
establish in all laboratories. In breast cancer, the PD-L1 relative expression
on tumor cells showed a signicantly higher predictive performance for
overall survival compared to the commonly used PD-L1 tumor propor-
tion score.
Disclosure Statement: e authors declare the following: e PD-L1 (MS-
VA-711R), the CTLA-4 (CTLA4/6864R), the CKpan (PAN-CK/4999R), the
Ki67 (MKI67/6517R), the CD31 (MSVA-031R) and the CD20 antibody clone
IGEL/1497R were provided from MS Validated Antibodies GmbH (owned by a
family member of GS).
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 11
Biomarker
Poster
79
EarlyCRP kinetics predict long-term treatment success and
favorable outcomes of anti-PD-(L)1 immune checkpoint
blockade in metastatic urothelial carcinoma
Niklas Klümper1,2; Danijel Sikic3; Jonas Saal4; Thomas Büttner1;
JonasJarczyk5; Philip Zeuschner6; Maximilan Weinke7; Charis Kalogirou7;
Johannes Breyer8; Maximilian Burger8; Philipp Nuhn5; Karl Tully9;
FlorianRoghmann9; Christian Bolenz10; Friedemann Zengerling10;
RalphWirtz11; Michael Muders12; Glen Kristiansen12; Jörg Ellinger1;
BerndWullich3; Michael Hölzel2; Arndt Hartmann13; Philipp Erben5;
Manuel Ritter1; MarkusEckstein13
1Universitätsklinikum Bonn, Klinik für Urologie, Bonn, Deutschland
2Universitätsklinikum Bonn, Institut für Experimentelle Onkologie, Bonn,
Deutschland
3Uniklinik Erlangen, Klinik für Urologie, Erlangen, Deutschland
4Universitätsklinikum Bonn, Medizinische Klinik III, Klinik für Hämatologie und
Onkologie, Bonn, Deutschland
5Universitätsklinikum Mannheim, Klinik für Urologie , Mannheim, Deutschland
6Universitätsklinikum des Saarlandes, Klinik für Urologie, Homburg, Deutschland
7Uniklinikum Würzburg, Klinik für Urologie, Würzburg, Deutschland
8Universität Regensburg, Klinik für Urologie, Caritas-Krankenhaus St. Josef,
Regensburg, Deutschland
9Ruhr-Universität Bochum, Klinik für Urologie, Marien Hospital Herne, Bochum,
Deutschland
10Universitätsklinikum Ulm, Klinik für Urologie, Ulm, Deutschland
11Stratifyer Molecular Pathology GmbH, Köln, Deutschland
12Universitätsklinikum Bonn, Institut für Pathologie, Bonn, Deutschland
13Uniklinik Erlangen, Institut für Pathologie, Erlangen, Deutschland
Background: Recently, Fukuda et al. described early on-treatment
C-reactive protein (CRP) kinetics in metastatic renal cell carcinoma that
predicted favorable treatment outcomes [1]. ese early CRP kinetics at
the onset of immunotherapy thus appear to be a promising predictive tool
for monitoring antitumor immune response, and here we aimed to inves-
tigate its potential for predicting ICB response in metastatic urothelial
carcinoma (mUC).
Methods: We conducted a multicenter observational retrospective study
comprising 154 patients with mUC treated with ICB to evaluate the pre-
dictive value of on treatment CRP kinetics. ree CRP kinetics groups
were dened: CRP are-responders (initial doubling of baseline CRP and
subsequent decrease below baseline), CRP responders (decrease of at least
30% of baseline CRP) and CRP non-responders. CRP kinetics groups
were correlated with baseline parameters, PD-L1 status (combined posi-
tivity score, CPS), progression-free (PFS) and overall survival (OS).
Result: Objective response according to RECIST v1.1 were observed in
57.1% of CRP responders, 45.8% of CRP are-responders and 17.9% of
CRP non-responders (P<0.001). CRP are-response was associated with
prolonged PFS and OS (P<0.001) while PD-L1 measured by CPS failed to
predict responses or outcomes. In multivariable Cox regression analysis,
CRP are-responders showed a risk reduction of ~70% for tumor progres-
sion an death compared to CRP non-responders.
Discussion: Future prospective studies with standardized CRP sampling
schedules are required to validate the predictive and prognostic CRP
are-response predicts ICB success value of CRP kinetics.
Conclusion: CRP (are-)responses robustly predict immunotherapy
response and outcomes in mUC independent of PD-L1 status. us, early
on-treatment CRP kinetics is a promising low cost and easy-to-implement
biomarker to optimize therapy monitoring in patients with mUC treated
with ICB.
Indication of source:
[1] PMID: 33602695
Disclosure Statement: e authors declare no conict of interest.
117
Claudin 18 Isoform Expression in Gastric Adenocarcinoma
andPancreatic Adenocarcinoma
Takeshi Saito1; Takashi Matsuda1; Diarmuid Moran1; Stefan Langhammer2
1Astellas Pharma, Inc., Northbrook, USA
2Astellas Pharma GmbH, München, Deutschland
Background: e claudin 18 (CLDN18) protein has two isoforms:
CLDN18.1 and CLDN18.2. CLDN18.2 is the dominant isoform expressed
in gastric adenocarcinoma (GA) and pancreatic adenocarcinoma (PA);
thus, it has emerged as a targetable biomarker. Zolbetuximab, a chimeric
IgG1 monoclonal antibody, binds specically to CLDN18.2 and mediates
cancer cell death via antibody-dependent cellular cytotoxicity and com-
plement-dependent cytotoxicity. Zolbetuximab study results highlight the
importance of selecting patients with CLDN18.2–positive cancer; how-
ever, CLDN18 isoforms are dicult to dierentiate at the protein level.
is study aimed to explore and conrm expression patterns of CLDN18
isoforms in a large dataset.
Methods: Relative CLDN18.1 and CLDN18.2 expression was analyzed
using bioinformatics mining of the TCGA database. TCGA RNA-Seq data
for GA (n=416) and PA (n=178) were analyzed for isoform expression
values by counting reads mapped on specic exons of both isoforms. Data
were expressed as fragments per kilobase of exon model per million reads
mapped (FPKM).
Result: Median expression values of CLDN18.2 and CLDN18.1 were 48.6
and 0.453 FPKM, respectively, in GA and 19.9 and 0.352 FPKM, respec-
tively, in PA. CLDN18.1 expression was below baseline (<0.5 FPKM) or
low (0.5-10 FPKM) in 95% of GA samples and in 100% of PA samples. In
contrast, CLDN18.2 was detectable above 10 FPKM in 69% of GA samples
and in 61% of PA samples with 38% and 16% of samples, respectively,
expressing CLDN18.2 ≥100 FPKM. A comparison of median isoform
expression in samples with CLDN18.1 expression detected above baseline
(>0.5 FPKM) demonstrated a 93-fold and 92-fold higher median expres-
sion of CLDN18.2 over CLDN18.1 in GA and PA, respectively.
Discussion: Results conrm that CLDN18.2 is the more dominantly
expressed isoform in a large dataset of GA and PA cases. Negligible
CLDN18.1 RNA expression suggests that meaningful protein expression
would not be anticipated.
Conclusion: ese results indicate that detection of total CLDN18 protein
is representative of CLDN18.2 expression in PA and GA.
Disclosure Statement: e authors declare the following: All authors are
employees of Astellas Pharma, Inc.
325
Biomarker panel predicts response to MEK inhibition in
colorectal cancer
Ulrike Pfohl1,2; Jürgen Loskutov1; Sanam Bashir3; Ralf Kühn4;
MarkusTemplin5,6; Gerrit Erdmann6,7; Soulafa Mamlouk8; Sergei Belanov9;
Christoph Reinhard1,6; Lena Wedeken1; Christian Regenbrecht1,6,10
1CELLphenomics GmbH, Berlin, Deutschland
2Goethe-Universität Frankfurt am Main, Frankfurt am Main, Deutschland
3BioNTech SE, Mainz, Deutschland
4MDC Berlin (Max-Delbrück-Centrum für Molekulare Medizin), Berlin,
Deutschland
5NMI Naturwissenschaftliches und Medizinisches Institut, Reutlingen,
Deutschland
6ASC Oncology GmbH, Berlin, Deutschland
7NMI TT GmbH, Berlin, Deutschland
8CharitéUniversitätsmedizin Berlin, Institut für Pathologie, Berlin, Deutschland
9Universität Helsinki, Helsinki, Finnland
10Universitätsmedizin Göttingen, Institut für Pathologie, Göttingen, Deutschland
Background: In colorectal cancer (CRC) mutations in the TGF-β/
BMP pathway, particularly in the SMAD4 gene have been correlated
with decreased overall survival and are suspected to be responsible for
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts12
chemoresistance (1, 2). erefore, there is a critical need for recogniz-
ing therapeutic agents, capable of targeting SMAD4 mutated tumors. In
the present study, we uncover the mechanistic role of SMAD4R361H using
oncoproteomics in syngeneic CRISPR-engineered SMAD4R361H CRC
patient-derived organoids (PDO).
Methods: We investigated multiple PDO from a single CRC tumor that
dier only by SMAD4R361H mutation. Using CRISPR-Cas9 approach, we
introduced R361H into SMAD4 wildtype PDO. Organoid cultures were
subjected to a comparative drug screening, RNA-Sequencing and subse-
quent multiplex protein proling analysis (DigiWest®).
Result: SMAD4R361H PDO were more sensitive to MEK inhibition com-
pared to their SMAD4 wildtype counterparts. Out of SMAD family
proteins, only SMAD5 showed changes in protein level and phosphor-
ylation status in response to MEK-inhibition, both were increased only
in SMAD4wt PDO. We tested over 50 CRC models and discovered up to
95% and 79% signicant positive prediction for the MEK inhibitors cobi-
metinib and trametinib, respectively, for models with disruption in the
TGF-β/BMP pathway.
Discussion: BMP signaling promotes cancer cell proliferation and tumor
growth (3). It is plausible to assume, that functional loss of SMAD4 and
thus loss of SMAD5 signaling render SMAD4R361H subpopulation of
cells more sensitive to MEK inhibitors. We propose to use the status of
SMAD4, ARID1A, BMPR2, and FBXW7 as a biomarker for considering
MEK inhibitors to achieve a clinical benet for cancer patients.
Conclusion: A disruption in the BMP pathway through loss-of- function
mutation or deletion in SMAD4, ARID1A, BMPR2, and FBXW7 is
responsible for the sensitivity towards MEK-inhibition in CRC.
References:
1. A. M. Sarshekeh et al., Plos One. 12, e0173345–e0173345 (2017).
2. M. Zhao, L. Mishra, C. X. Deng, Int J Biol Sci. 14, 111–123 (2018).
3. J. Peng et al., Mol Carcinogen. 55, 335–45 (2015).
Disclosure Statement: e authors declare no conict of interest.
385
The App “Präzisionsonkowissen - Pow”: State of the Art
Precision Oncology – combining scientic and clinical
knowledge
Tanja Grimmig1; Carine Nguemeni1; Sarah Schuster1; Friedrich Schütze1;
Christina Jessen1; Viktoria von Krosigk1; Thomas Spall2; Erik Belleville2;
Friedrich Overkamp2
1ClinSol GmbH & Co. KG, Würzburg, Deutschland
2onkowissen.de GmbH, Würzburg, Deutschland
Precision oncology is evolving at a fast pace and has entered the main-
stream of clinical practice. It is dened as the molecular proling of
tumors to identify targetable alterations. is allows for a personalized
treatment based on matching biomarkers and individual characteristics of
the patients cancer to targeted molecular therapies. With the treatment of
cancer moving from traditional approaches towards precision medicine,
the need for in-depth scientic knowledge about this eld is continuously
growing as well as up-to-date information regarding available therapeutic
options.
e universal app “Präzisionsonkowissen” (aka Pow) supports this
transition by oering a broad spectrum of useful information/tools for
everyday clinical practice. Pow contains relevant back-ground informa-
tion about the individual biomarkers, their function and biological signif-
icance in oncology.
A specic chapter covers innovative approaches to comprehensive
molecular, cellular and functional analysis of the alteration status of
tumors. Analytical methods and concepts are particularly highlighted,
including multimedia insights into clinical pathology. e app also pres-
ents the latest approved biomarker-targeted standard therapies, in con-
formity with evidence-based guidelines and approval studies. Further, a
particular focus is on new options for targeted treatments including o/
no-label therapies and therapies in an advanced stage of development. A
special feature is the newsfeed, which informs the user about novelties in
the eld, such as relevant studies or new EMA/FDA approvals. Finally,
Pow oers the possibility to dene favorites and to create a personalized
quick access to the most relevant content of the respective chapters.
Pow is an innovative, interactive and educational app database collec-
tion of high-grade information on precision oncology. It supports clinical
daily routine including the preparation for molecular tumor boards and
the feature of keeping up-to-date in best-practice therapies, as well as in
o-label/no-label treatments.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
446
Detection of cfHPV16-DNA in liquid biopsy - A promising
biomarker for patients with HPV-related oropharyngeal
squamous cell carcinoma
Nora Würdemann1; Christina Alidousty2; Oliver Siefer1; Rishabh Jain1;
Christian Ulrich Hübbers1; Ste Silling3; Darius Schagh4; Robin Bacher5;
Henrike Reder6; Reinhard Büttner2; Markus Dietlein5; Alexander Drzezga5;
Marc Schlamann4; Ulrike Wieland3; Alexander Quaas2; Claus Wittekindt7;
Ernst-Jan Speel8; Steen Wagner6; Anne Schultheis2; Jens Peter Klußmann1
1Klinik und Poliklinik für Hals-, Nasen- und Ohrenheilkunde, Uniklinik Köln, Köln,
Deutschland
2Institut für Pathologie, Uniklinik Köln, Köln, Deutschland
3Institut für Virologie, Uniklinik Köln, Köln, Deutschland
4Institut für Diagnostische und Interventionelle Radiologie, Uniklinik Köln, Köln,
Deutschland
5Klinik und Poliklinik für Nuklearmedizin, Uniklinik Köln, Köln, Deutschland
6Klinik und Poliklinik für Hals-, Nasen- und Ohrenheilkunde, Uniklinik Gießen,
Gießen, Deutschland
7Klinik für Hals-Nasen-Ohrenheilkunde, Klinikum Dortmund, Dortmund,
Deutschland
8Institut für Pathologie, Uniklinik Maastricht, LK Maastricht, Netherlands Antilles
Background: Incidences of oropharyngeal squamous cell carcinoma
(OPSCC) associated with high-risk Human Papillomavirus (HPV) are
steadily increasing worldwide. Although HPV-related OPSCC are accom-
panied by a signicantly better 5-year overall survival compared with
HPV-negative OPSCC, 25% still develop locoregional recurrence or dis-
tant metastases. Biomarkers to monitor therapy response and disease pro-
gression are lacking to this point.
Methods: In a multicenter study, the concentration of cell-free (cf)
HPV16-E6/E7 DNA in plasma was measured by quantitative (q)PCR /
droplet digital (dd)PCR at initial diagnosis and during follow-up in
patients with OPSCC (test-cohort n = 37; validation-cohort n = 53). e
copy number (cn) of cfHPV16-E6/E7 DNA in plasma was subsequently
correlated with the course of disease as well as imaging and clinicopatho-
logical parameters.
Result: In the test-cohort, ROC-Analysis revealed an outstanding dis-
crimination in ddPCR (AUC = 0.9256) and qPCR (AUC = 0.9467).
Furthermore, elevated cfHPV16-DNA E7 cn detected by ddPCR cor-
related with higher T-stage (p ≤ 0.050). In our validation-cohort, ROC-
Analysis revealed discrimination only in E6-ddPCR and no correlation
of median cfHPV16-DNA cn with T- or N-stage was detected in either
PCR method. Nevertheless, cfHPV16-DNA cn correlated with metabolic
tumor volume in 18F-FDG-PET-CT (r = 0,5982; R2 = 0,3578; p = 0,0012).
A signicant reduction of cfHPV16 E6 DNA levels was detected in both
cohorts post-therapeutically (p ≤ 0.001), whereas an increase in copy
number correlated with recurrence or distant metastasis.
Discussion: ddPCR demonstrated to be more sensitive than qPCR for
the detection of cfHPV16-DNA in plasma of patients with HPV-related
OPSCC and tumor stage and metabolic tumor volume inuence the
amount of cfHPV16-DNA shed into the blood stream.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 13
Conclusion: cfHPV16-DNA in plasma of patients with HPV-associated
OPSCC represents a promising biomarker for monitoring the course of
disease. Prospective studies with larger cohorts are needed to validate
these results.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
568
Decreased expressions of CD44v4 and CD44v10 correlate with
earlier tumor progression
Michael Modrok1; Undine Tiller1; Rosa Rühl1; Peter Baumgarten1;
ChristianSenft1; Arend Koch2; Jan Walter1,3; Diana Freitag1
1Department of Neurosurgery, University Hospital Jena, Jena, Deutschland
2Department of Neuropathology, Charitè - Universitätsmedizin Berlin, corporate
member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin,
Deutschland
3Department of Neurosurgery, Medical Center Saarbruecken, Saarbrücken,
Deutschland
Background: e transmembrane glycoprotein CD44 is widely used to
identify tumor stem cells (CSCs). However, CD44 controls a variety of
processes, making the identication of CSCs very dicult. Due to alter-
native splicing, there are 10 variable forms of CD44 (CD44v1-v10) besides
the stable form CD44s, each with dierent properties in tumor biology.
e aim of this study was to evaluate the expression of dierent CD44
isoforms in human meningiomas and to assign specic cell properties to
their expressions by correlation with clinical data.
Methods: RNA was isolated from 80 specimens of individual meningioma
patients and analyzed by quantitative polymerase chain reaction (qPCR).
Expression of CD44s as well as CD44v1-v10 was analyzed. e correla-
tions of the expression data with the clinical data was analyzed in terms of
progression-free survival (PFS) at a monitoring interval of 2 years (n=68)
aer prior ROC analysis (Kaplan-Meier).
Result: Gene expressions from CD44v3 to CD44v10 were found in the
majority of samples. Only for CD44s and CD44v3, higher relative expres-
sion values could be detected in meningiomas as compared to control
tissue (dura mater). However, subgroup analyses revealed that the mean
relative expressions for CD44 variants v4, v5, v7, v8 and v9 and v10
showed signicant dierences between WHO grade I or II and control
tissue. Subsequent Kaplan-Meier analysis for PFS indicated that high
expression levels of the v4 and v10 isoforms were associated with better
outcome, particularly in male patients.
Discussion: ese analyses provide rst hints at a possible involvement of
the individual CD44 isoforms in the progression of human meningiomas.
In addition, there is evidence that the v4 and v10 isoforms play a protec-
tive role in tumor progression.
Conclusion: CD44 isoform expression may potentially aect tumor pro-
gression in meningiomas, rendering them a potential target for therapeu-
tic approaches in meningioma treatment.
Disclosure Statement: e authors declare no conict of interest.
586
Serum proteins as predictive markers of the response to
neoadjuvant chemotherapy for breast cancer
Ines Derya Steenbuck1; Miguel Cosenza2; Klemens Fröhlich2;
Bettina Mayer3; Tilman Werner2; Markus Jäger1; Daniela Weiß1;
Claudia Noething1; Oliver Schilling2; Thalia Erbes1
1Department of Obstetrics and Gynecology, Medical Center - University of
Freiburg, Freiburg, Deutschland
2Institute of Surgical Pathology, Medical Center - University of Freiburg, Freiburg
3Institute of Molecular Medicine and Cell Research , University of Freiburg,
Freiburg, Deutschland
Breast cancer continues to be the most common cancer type among
women in Germany and worldwide. Over the last years neoadjuvant
chemotherapy NACT represents an increasingly important role as a
standard therapy-regimen . Because of the correlation of pathological
complete response (pCR) and long-term clinical prognosis there is a need
to monitor therapy-response in term of therapy adaption. Until now,
breast-ultrasound represents the method of choice for progress-evalua-
tion during NACT. In this proof-of-concept, retrospective longitudinal
cohort study, we had the purpose to nd an additional method for ther-
apy-response validation by liquid biopsy. Serum samples from patients
suering from breast cancer of the subtype Luminal B (Her2/neu -) and
TNBC were examined during NACT with 4x epirubicin and cyclophos-
phamide (EC)+ 12x paclitaxel. 11 complete responders (CR) with pCR
and 11 non-responders (NR) with non-pCR, >ypT0, were included. In
addition to, 24 sera from healthy women were also included as a control
group. Samples were taken before the rst cycle of EC (t0), before the third
cycle of EC (t1) and before the third cycle of Paclitaxel (t3). As method of
choice, we used immunoanity depletion of 14 high abundant proteins,
followed by Lys-C + Trypsin Co-digestion, clean up, isobaric labelling,
fractionation by high-pH reversed-phase liquid chromatography, and
LC-MS/MS-measurement. We were able to demonstrate a signicant
reaction to the NACT in the proteomic prole at timepoint t1 and t3 com-
pared to timepoint t0. Furthermore, 5 potential marker candidates were
identied, which show a dierent intensity behaviour between the groups
NR and CR (HGF receptor, N-cadherin, Centrosomal protein 192 kDa,
Contactin 1, Cholinesterase). N-cadherin should be emphasized, due
to an inverse behaviour with an increase of intensity at t1 in CR and a
decrease of intensity at t1 in NR. e present ndings lay the foundation
to expand the study with a larger patient number.
Disclosure Statement: e authors declare no conict of interest.
661
Kidney cancer urine marker
Barbara Köditz; Jochen Fries; Jan Herden; Manuel Huerta;
AxelHeidenreich; Melanie von Brandenstein
Uniklinik Köln , Urologie, Köln, Deutschland
Background: : Recently, our group showed that Vim3 is overexpressed in
tissue samples of renal oncocytomas and Mxi-2 in clear cell renal carci-
noma (ccRCCs). e mechanism leading to the truncation of both pro-
teins is known and involves with two miRs, both detectable in urine. Since
the analysis of miRs is time consuming, our aim was to identify the trun-
cated proteins in urine instead. Furthermore, urine samples from small
renal cancers (SRM) (n=45, <4 cm) were analyzed to get a pre-surgical
dierentiation of the cancer subtypes.
Methods: Urines were accessed from the urological biobank (n=350).
Proteins were isolated from urine samples, and Western blots were per-
formed. Each sample was analyzed with ELISA for the expression of Vim3
and Mxi-2. A lateral ow assay was established. For the detection of SRMs,
the miRs were isolated and qRT-PCR was performed.
Result: A signicant increase of Vim3 in urines from patients with onco-
cytoma (n=20) was detectable with ELISA compared to all other subtypes
of RCCs (chromophobe (n=50), papillary (n=40), ccRCC (n=200), and
controls (n=40) (***p<0.0001)). Mxi-2 was predominantly overexpressed
in ccRCCs (***p<0.0001). Lateral ow assay of Vim3 and Mxi-2 shows
two bands in the case of oncocytoma and ccRCC indicating the specicity
of this test. For SRMs, an overexpression of miR-15a/Mxi2 was detectable
in urine samples from ccRCC and chromoRCC patients. In contrast to
that miR-498/Vim3 were predominantly overexpressed in oncocytoma
patients.
Discussion: Here two dierent expression patterns were identied based
on the type of kidney tumour. Also the size of the kindey tumor do not
play a role in the signicant of the data.
Conclusion: Both proteins (Vim3 and Mxi-2) were detectable in patients
urines and can be used for the non-invasive dierentiation of kidney
cancers.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts14
669
Assessment of genetic tumor proles and clonal evolution
byliquid biopsy: The Augsburger Longitundinal Plasma
Study(ALPS)
Sebastian Sommer1; Maximilian Schmutz1; Sebastian Dintner2;
Maria Campillo1; Maria Eberle1; Yvonne Silber1; Angela Langer2;
Bruno Märkl2; Matthias Schlesner3; Simone Hummler1; Boris Kubuschok1;
Martin Trepel1; Rainer Claus1
1Universitätsklinikum Augsburg 2. Medizinische Klinik, Augsburg, Deutschland
2Universitätsklinikum Augsburg, Institut für Pathologie und molekulare
Diagnostik, Augsburg, Deutschland
3Institut für Informatik , Biomedizinische Informatik, Data Mining und Data
Analytics, Augsburg, Deutschland
Background: Analyzing circulating tumor DNA (ctDNA) from liquid
biopsy (LBx) allows diagnostic and prognostic assessment and disease
course monitoring of malignancies. However, the clinical application
of ctDNA assessment is still limited. ALPS is a trial and a LBx-banking
resource that aims at bridging the gap of LBx from translational research
to routine clinical practice by investigating key questions: (a) the concor-
dance of LBx and tissue biopsy (TBx); (b) the relevance of LBx for fol-
low-up and disease progression; (c) the applicability of LBx to display
clonal heterogeneity and evolution upon treatment and progression.
Methods: ALPS is a prospective observational study of an anticipated
number of n=1000 patients (pts) over 4 years with metastatic cancers. At
time of enrollment, tumor TBx and initial LBx from peripheral blood (PB)
are obtained. Serial PB samples are collected every 3 months concurrently
with standard staging evaluations. Circulating cell free DNA (ccfDNA) is
analyzed using CAPP-seq. Genomic characterization of tumor TBx and
controls is performed by WES.
Result: Recruitment started in April 2021, 86 patients have been enrolled
in the pilot phase. Median age is 63 years (range 29-89), 27% are women.
Pts with NSCLCs were most common (n=17), followed by SCLC (n=8),
pancreatic (n=7) and colon cancer (n=5), CUP (n=5), esophageal cancer
(n=5), and other entities. ccfDNA was isolated from 91 plasma samples of
78 pts. ccfDNA amounts ranged from 0,24 ng to 12,96 µg. Sequencing of
ccfDNA from the rst 8 pts yielded46 to 68M reads with an on-target rate
of 40-80% and a detection sensitivity of 0.1%. Cancer-related mutations
and CNVs were identied in all 8 samples.
Conclusion: Here we describe a study and infrastructural resource
(ALPS) for the systematic evaluation of LBx in metastatic tumors. In the
the pilot phase, we demonstrate that ccfDNA can be obtained in sucient
quantity and quality for successful genomic analyses in patients with dif-
ferent metastatic malignancies. e design of ALPS is suitable to address
questions relevant to routine clinical application of LBx.
Disclosure Statement: e authors declare no conict of interest.
680
In-depth methylation analysis of the epigenetic marker
regions ASTN1, DLX1, ITGA4, RXFP3, SOX17 and ZNF671
incervical precancerous lesions and cervical carcinoma
Lars Jansen1; Katrin Beer1; Martina Schmitz2; Alfred Hansel2;
Ingo B. Runnebaum1; Matthias Dürst1
1Gynäkologische Molekularbiologie, Universitätsklinikum Jena, Klinik und
Poliklinik für Frauenheilkunde und Fortpanzungsmedizin, Jena, Deutschland
2oncgnostics GmbH, Jena, Deutschland
Background: Cervical carcinoma is the fourth most common cancer in
women worldwide. In carcinogenesis, local DNA hypermethylation oen
occurs in cytosine- and guanine-rich DNA regions called CpG islands,
which are frequently located in promoter regions. e aim of this work
was to investigate the extent to which methylation of CpG islands associ-
ated with the genes ASTN1, DLX1, ITGA4, RXFP3, SOX17 and ZNF671,
can be attributed to tumor or dysplastic cells and thus represent a direct
phenomenon of cervical carcinogenesis.
Methods: From deep-frozen tissue sections, 30 carcinomas and 18 CINs,
tumor and dysplastic cells, respectively, as well as adjacent stroma cells
were manually microdissected. Chemical bisulte treatment was used to
convert the methylation information into a sequence dierence. rough
bisulte-specic PCR the DNA regions of interest were amplied, and
methylation within these regions was determined via next-generation
sequencing.
Result: Depending on marker regions, methylation in tumor cells was 6-
to 57-fold higher than in stromal cells. In tumor areas methylation was
> 70% for the marker regions ASTN1, DLX1, SOX17, and ZNF671 and
> 47% for ITGA4 and RXFP3 in the sample set tested. In contrast, stro-
mal cell methylation is ≤ 4.1% for ASTN1, ITGA4, RXFP3, SOX17 and
ZNF671 markers. DLX1 showed a signicantly higher baseline methyla-
tion of 14.2%. In addition, DNA methylation was shown to increase with
the severity of cervical lesions, from average of 5.6% in CIN1, to 8.6% in
CIN2, to 22.5% in CIN3.
Discussion: Methylation changes in the six marker regions ASTN1, DLX1,
ITGA4, RXFP3, SOX17 and ZNF671, the detection of which provides the
basis for the molecular cancer diagnostic GynTect, indeed occurs in the
dysplastic and the tumor cells, not in the surrounding tissue.
Conclusion: Methylation of the six marker regions is at least a conse-
quence of, if not even the cause for cervical carcinogenesis.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
698
Vim3 – a new surrogate marker for prostate cancer
Melanie von Brandenstein; Barbara Koeditz; Jochen Fries;
Axel Heidenreich
University Hospital of Cologne, Clinic and Polyclinic for Urology, Cologne,
Deutschland
Background: Prostate cancer (PCa) is the most frequently diagnosed
malignancy in elderly men. e determination of Vim3 in patients’ serum
can be an important new biomarker for the determination of the biologi-
cal aggressiveness of PCa. In our opinion, the measurement of Vim3 levels
in the serum might predict the aggressiveness and prognosis of PCas.
Methods: We reviewed serum samples from 350 male patients during the
years 2015 to 2018 from our department. Control group: patients without
cancer background, median PSA < 4.0 ng/ml. Low risk group: Gleason 6,
median PSA 7.4 ng/ml. Intermediate risk group: Gleason 7a-7b, median
PSA 14.9 ng/ml. High risk group: Gleason >8, median PSA 30.4 ng/ml
without visible metastases on routine imaging studies such as Bone scan
and CT scans of the abdomen and the small pelvis. Metastasis group:
patients with osseous or visceral metastasis at time of rst diagnosis,
median PSA 64.4 ng/ml. Recurrence group: patients with recurrence (PSA
relapse and metastasis), median PSA 41.3 ng/ml. Vim3 ELISA was estab-
lished previously and performed with 50 µl patient serum.
Result: Via ELISA it could be demonstrated that the Vim3 protein level
increased signicantly (p<0.001) with increasing biological aggressiveness
of human PCa specimens from prostate biopsies and/or radical prostatec-
tomy specimens (Gleason ≥8, independent of the pT stage). Furthermore a
clear cut-o value for Vim3 level was determined(cut-o 300-350ng/ml).
Discussion: Vim3 could be a new biomarker for PCa, especially for PCa
with increasing metastatic potential. In our opinion, Vim3 values above
a predetermined cut of level could support the suspicion of a high grade
PCa even if PSA and Gleason grade aer biopsy do not (yet) indicate the
presence of a high grade PCa.
Conclusion: Serum Vim3 levels rise with increasing malignancy of the
prostate cancer and correlate with the Gleason Score and therefore could
be usable as novel surrogate marker for prostate cancer
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 15
701
EBV induced regulation mechanism in metastasized
and non-metastasized seminoma
Barbara Köditz1; Yasmine Maatoug1; Tim Nestler1; Jochen Fries1;
PiaPaenholz1; David Nicol2; Axel Heidenreich1;
Melanie von Brandenstein1
1Uniklinik Köln , Urologie, Köln, Deutschland
2The Royal Marsden NHS Foundation Trust, Consultant Urological Surgeon,
London, Vereinigtes Königreich
Background: Epstein-Barr Virus (EBV) has the ability to induce a regula-
tion mechanism that results in the down regulation of the truncated ver-
sion of Vimentin 3 (Vim3), a metastasizing marker. e presence of EBV
is responsible for the upregulation of miRNA 199-3p, which downregu-
lates Endothelin-1 (ET-1) by binding its 3’ UTR. ET-1 induces the produc-
tion of Vim3. Since the described regulation mechanism was identied in
clinical stage I seminomas with uneventful follow-up we hypothesized an
opposite mechanism will occur in metastasized seminomas.
Methods: For the investigation of the regulation mechanism tissue biop-
sies from primary orchiectomy specimens with pure, classic seminoma
of clinical stage IIC/III patients and from resected retroperitoneal lymph
node metastases of clinical stage IIA/B seminoma patients were analysed.
Total RNA was isolated from macrodissected paran embedded tissue
areas. e expression of the miRNA 199-3p, EBNA-1, ET-1 and Vim3 was
determined via qRT-PCR. Furthermore, the expression of EBER-1 and
Vim3 was analyzed via immunohistochemistry.
Result: Via immunohistochemistry and qRT-PCR no EBER expression
was present in primary tumors and lymph node metastases. Furthermore,
down regulation of the miRNA 199-3p and an up regulation of ET-1 and
Vim3 were detectable.
Discussion: In case of metastasized seminoma no EBV infection was
detectable neither in the tumor sample nor in metastases which resulted
in an increased expression of ET-1 and Vim3 and downregulation of
miR-199 contributing to the metastatic process of pure seminomas.
Prospective validation of these ndings is under way to proof that those
molecular events might be used as a biomarker for high risk disease
triggering adjuvant therapy following radical orchiectomy. Whether the
upregulation of the miR-199 can be used as metastasizing inhibitor needs
to be evaluated further.
Conclusion: To summarize a regulation mechanism induced by EBV
wasidentied.
Disclosure Statement: e authors declare no conict of interest.
708
A new signal transduction pathway for AR in urothelial
carcinoma
Melanie von Brandenstein1; Julie Brunner1; Barbara Koeditz1; Manuel
Huerta1; Maximillian Schmautz1; Axel Heidenreich1
1University Hospital of Cologne, Clinic and Polyclinic for Urology, Cologne,
Deutschland
Background: Since, it is already known that bladder cancers with elevated
endothelin-1 (ET-1) levels have a higher metastasizing potential. For the
early detection of urothelial carcinoma, the analysis of elevated levels of
molecules in the patients’ blood or urine is of great interest. Our group
could recently show that patients with a muscle invasive bladder cancer
(MIBC) have higher levels of ERß in the blood.
Methods: e urinary bladder cancer cell line HTB-9 were cultivated as
recommended and treated with ET-1 and ET-1 receptor blockers (BQ123
and BQ788). Pull down assays with the androgen receptor (AR) and the
miR-708 were performed. Western Blot aer dierent treatment options
and qRT-PCR were established. Furthermore, we analysed via ELISA
urine samples from patients with bladder cancer (n=35) and control
healthy donors (n=15).
Result: In HTB-9 cells, we identied a novel mechanism, which is respon-
sible for the E-cadherin downregulation in urothelial carcinoma. ET-1
forms a complex with the AR in the cytoplasm and migrates into the
nucleus. e newly identied complex is important for the transcription
of the estrogen receptor beta (ERß). We were able to show that the ERß
overexpression leads to an increased expression of miR-708. It is known,
that this miR can bind to the 3’UTR of E-cadherin and acting as onco-miR.
Discussion: We identied an ET-1 dependent mechanism leading to the
overexpression of specic biomarkers and the downregulation of tumor-
genes in urinary bladder cancers. In urine samples, a signicant overex-
pression of ET-1 and ERß and a resulting downregulation of E-cadherin
was detectable in bladder cancer patients.
Conclusion: e analysis of such biomarkers could be probably used in
future for the evaluation of urothelial carcinoma.
Disclosure Statement: e authors declare no conict of interest.
777
Clinically relevant prognostic biomarkers for immune
checkpoint inhibitor therapy in NSCLC
Gloria Zeitler1; Wolfgang Brückl1; Joachim Ficker1
1Klinikum Nürnberg Nord, Nürnberg, Deutschland
Background: We investigated the association of clinical and laboratory
ndings with response and treatment eects in immune-checkpoint
inhibitor (ICI) therapy treated advanced NSCLC patients.
Methods: NSCLC patients receiving at least one dose of ICI therapy at the
Lung Cancer Center Nuremberg between 2016 and 2019 were identied
retrospectively. Factors associated with PFS or OS were assessed with Cox
proportional hazard models. A prognostic score (∆-Score) combining
∆LDH, ∆CRP and ∆G-GT created and categorizes patients into prognos-
tic subsets.
Result: Among 89 patients, 66.3% were men, median age was 68 years
and 70.8% received pembrolizumab as 1st line treatment. For the whole
cohort, median PFS and OS was 5 months and 11.2 months, respectively.
Median PFS was 5.7 months and median OS was 12.7 months in the 1st
line therapy cohort. On multivariate analysis, an increasing ∆LDH (p =
0.043), NLR < 5 (p = 0.045) and CRP-Q1 (≤ 7.7 mg/dL) (p = 0.033) were
signicantly associated with superior median PFS. CRP-Q1 was also asso-
ciated with a greatly enhanced median OS for the whole cohort. A low
∆-Score reached a high level of signicance in terms of PFS and showed a
clear trend regarding OS.
Discussion: ere are several limitations to this study, e.g. the cut-o val-
ues of the laboratory ndings were not adapted to patients‘ gender and
chosen by using the standards determined by the local laboratory without
investigating their devisive character.
Conclusion: Our results demonstrate that laboratory measurements
are eective tools in the prediction of response and outcome in NSCLC
patients treated by ICI. Further studies are warranted to conrm their
prognostic signicance in this patient population.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts16
990
Antitumor activity of dostarlimab by PD-L1 and tumor
mutation burden (TMB) in patients (pts) with mismatch repair
decient and procient (dMMR and MMRp) tumors in the
GARNET trial
Arndt Vogel1; Thierry André2; Susana Banerjee3; Dominique Berton4;
SusanL. Ellard5; Begoña Jimenez6; Vanessa Samouelian7; Lucy Gilbert8;
Valentina Boni9; Xinwei Han10; Grace Antony11; Jennifer Veneris10;
AnaOaknin12
1Leitender Oberarzt der Klinik für Gastroenterologie, Hepatologie,
Endokrinologie, Medizinische Hochschule Hannover, Hannover, Deutschland,
2Sorbonne University and Saint-Antoine Hospital, Paris, Frankreich
3The Royal Marsden NHS Foundation Trust and Institute of Cancer Research,
London, Vereinigtes Königreich
4GINECO & Institut de Cancerologie de lOuest
5BC CancerKelowna, Kelowna, Kanada
6Hospital Clínico Universitario Virgen de la Victoria, Malaga, Spanien
7Centre Hospitalier de lUniversité de Montréal, Montréal, Kanada
8McGill University Health Centre, Montréal, Kanada
9Hospital Universitario HM Sanchinarro [Aliation at the time of study, current
aliation Universitario Quironsalud], Madrid, Spanien
10GlaxoSmithKline, Waltham, MA, USA
11GlaxoSmithKline, London, UK
12Vall dHebron University Hospital, Barcelona, Spanien
Background: We report a post-hoc analysis of antitumor activity by pro-
grammed death-ligand 1 (PD-L1) expression and TMB in pts with dMMR
and MMRp advanced/recurrent (A/R) solid tumors, assessed in the
GARNET (NCT02715284) Phase I, multicenter, open-label, single-arm
study of PD-1 inhibitor dostarlimab.
Methods: 3 cohorts enrolled pts based on MMR status: dMMR (A1)
and MMRp (A2) A/R EC, and dMMR non-EC solid tumors (F). Pts
received dostarlimab 500 mg IV Q3W for 4 cycles, then 1000 mg IV Q6W
until progression/discontinuation. Exploratory biomarkers were TMB
(Foundation One test; high [TMB-H] ≥10 mutations/Mb) and PD-L1
(combined positive score [CPS] by Ventana assay; high [PD-L1-H]: CPS
≥1). Study not powered to assess antitumor activity within subgroups.
Result: TMB-H and PD-L1-H were common in dMMR solid tumors
(164/209 [78.5%] and 108/209 [51.7%], respectively); PD-L1-H was
observed in 39.4% (56/142) of MMRp EC tumors. Objective response
rate (ORR) (95% CI), per RECIST v1.1 assessed by blinded independent
central review, was higher in pts with TMB-H/PD-L1-H tumors (n=99;
55.6% [45.2–65.5]) than pts with TMB-low (L)/PD-L1-L tumors (n=51;
7.8% [2.2–18.9], respectively), or pts with TMB-L/PD-L1-H (n=57; 17.5%
[8.7–29.9]) or TMB-H/PD-L1-L tumors (n=32; 25% [11.5–43.4]). ORR
(95% CI) was 44.7% (34.9–54.8), 38.7% (29.4–48.6), and 13.4% (8.3–20.1)
for Cohorts A1, F and A2, respectively. Safety previously reported.1
Discussion: -
Conclusion: PD-L1-H and TMB-H were frequently observed in dMMR
cohorts, regardless of tumor type. PD-L1-H was also prevalent in MMRp
EC tumors. Although not powered to assess antitumor activity, ORR was
higher in pts with TMB-H and PD-L1-H solid tumors. Across cohorts,
dMMR status was predictive of response.
Indication of source: GSK 213346. Editorial support provided by
Fishawack Health, funded by GSK. Abstract originally presented at
AACR; New Orleans, LA; Apr 8–13, 2022 (#5135) and published in AACR
Proceedings. Reused with permission. Presented on behalf of the original
authors with permission.
Reference:
Andre T et al. Ann Oncol 2021;32(suppl 5):S829–S866.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
1035
The prognostic signicance of PDL-1 on circulating tumor cells
in gastrointestinal tumors
Leonie Konczalla1,2; Leon Kusterer1; Anna Wöstemeier3; Sabine Riethdorf4;
Nathaniel Melling1; Klaus Pantel4; Jakob Izbicki1; Matthias Reeh1
1University Medical Center Hamburg-Eppendorf, Departement of General,
Visceral and Thoracic Surgery, Hamburg, Deutschland
2University Medical Center Hamburg-Eppendorf, Mildred Scheel
Nachwuchszentrum, HaTriCS4, Hamburg, Deutschland
3University Hospital Bonn, General, Visceral-, Thoracic and Vascular Surgery,
Bonn, Deutschland
4University Medical Center Hamburg-Eppendorf, Tumor Biology, Hamburg,
Deutschland
Background: Individual cancer cells can escape from the primary tumor
to the bloodstream, where many immune cells are present. To date, the
immune escape mechanisms of these circulating tumor cells (CTCs) are
poorly understood, but there is an urgent need since exploring the key
mechanisms of CTC surveillance may lead to new therapeutic strategies
to prevent cancer cell proliferation, metastasis, and tumor recurrence.
We hypothesize that one mechanism is the expression of co-inhibitory
receptors such as PDL-1, which lead to decreased immune cell activity
and thereby immune escape of CTCs.
Methods: CTC detection by CellSearch and PBMC characterization by
multiparametric FACS analysis of 81 GI cancer patients with dierent
TMN stage.
Result: In total, 17,28% of all screened patients, CTCs were detected and
35,71% of the CTCs showed robust PDL-1 expression. Interestingly, all
of the PDL-1+ CTC patients appeared with distant metastases or local
recurrence, while patients with PDL-1- CTCs showed smaller frequency
of had distant metastases with only 44,4%. However, PDL-1+ CTC patients
occur to have higher frequency of PBMCs with especially signicantly
upregulated frequency of regulatory T cells (TREG). Moreover, we could
detect a higher expression of PD-1 on cytotoxic CD8+ T cells and tumor
fosteringTREG.
Discussion: Expression of PDL-1 on CTCs appears as a prognostic marker
for enhanced metastasis and thereby reduced outcome. is could be
explained by a PDL-1/PD-1 mediated tumor escape of CTCs in the blood
stream. Whether the expression con PDL-1 on CTCs and primary cancer
and metastasis tissue needs further investigation. However, addressing the
PDL-1/PD-1 axis by immunotherapy could help to reduce CTCs and their
metastatic potential.
Conclusion: PDL-1+ CTCs can be used as prognostic marker in GI can-
cer patients. Furthermore, immunotherapies may be able to reduce the
metastases in these patients.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 17
1052
Neurolament als Biomarker für sensorische Störungen
beiPatienten unter Chemotherapie
Clara Kalweit1; Tobias Bleumer1; Wolfgang Böhmerle2,3;
SebastianStintzing1; Lars Uwe Stephan1; Uwe Pelzer1
1Department of Hematology, Oncology and Tumorimmunology, Charité
Campus Mitte, Charité - Universitätsmedizin Berlin, Corporate Member of Freie
Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health,
Berlin, Deutschland
2Charité - Universitätsmedizin Berlin, corporate member of Freie Universität
Berlin and Humboldt Universität zu Berlin, NeuroCure Cluster of Excellence,
Berlin
3Department of Neurology, Charité Campus Mitte, Charité - Universitätsmedizin
Berlin, Corporate Member of Freie Universität Berlin, Humboldt- Universität zu
Berlin, and Berlin Institute of Health
Purpose: Polyneuropathies are common side eects in pts undergoing
polychemotherapy with signicant impact on pts’ quality of life. e axo-
nal structural protein neurolament is released in the context of neurode-
generative processes. e aim of the study is to evaluate the neurolament
as a biomarker for sensory disorders.
Methods: At the end of data collection, 100 pts with gastroenterological
cancer and lymphomas will be enrolled in our prospective trial. Pts will
have blood drawn prior to initiation, during and aer therapy, and at 6
and 12 months follow-up. In parallel, nerve conduction velocity (ENG) at
the peroneal nerve will be measured. To detect objectively neuropathies.
In order to record subjectively describe neuropathies, we check at each
examination appointment the quality of life using a modied question-
naire EORTC-QLQC30.
Results: As of April 2022, 51 out of 100 pts have been investigated.
Initially, the mean value of pts without carcinomatous meningitis for the
neurolament was 23,03 pg/ml. For the second examination date, 23 pts
have been included, the mean value was 49,67 pg/ml. 6 pts were examined
a 3rd time, the mean value was 47,2 pg/ml. In parallel, there is an increase
in the TNSr score in ENG from 1.7 points to 6.3 points from the rst to the
3rd examination. Initially, 6 pts already described par- and dysesthesias
in hands and feet. At the 2nd appointment, 22 pts reported moderate to
severe parand dysesthesias in hands and feet. 10 pts still reported tingling,
numbness, and insensations in the hands and feet at the 3rd examination.
Full recruitment is expected in September 2022.
Conclusion: Our study underlines the relevance of early diagnosis of
polyneuropathies as 22 of 51 pts develop moderate to severe paresthesias
and dysesthesias under polychemotherapy. At this point we are not able to
predict signicances regarding the potential biomarker. Now, the data are
not robust enough to perform subgroup analysis. In perspective, however,
the ability to predict polyneuropathies using neurolament will increase
as the amount of data increases.
Disclosure Statement: e authors declare no conict of interest.
1053
Patterns of trophoblast cell surface antigen 2 (TROP2) and
epithelial cell adhesion molecule (EPCAM) expression in
human tumors: A tissue microarray study on 14,766 tumors
Claudia Hube-Magg; David Dum; Ronald Simon; Elena Bady;
TimMandelkow; Maximilian Lennartz; Guido Sauter; Sarah Minner;
Andreas M. Lübke
Universitätsklinikum Hamburg-Eppendorf, Pathologie, Hamburg, Deutschland
Background: Trophoblast cell surface antigen 2 (TROP2) and epithelial
cell adhesion molecule (EPCAM) are cell surface receptors that play a role
in growth signal transduction and cell adhesion. Antibody drug conju-
gates against both proteins are approved or under development.
Methods: To comprehensively study expression patterns of TROP2 and
EPCAM in tumors, a tissue microarray containing 14’766 samples from
120 dierent tumor types was analyzed by immunohistochemistry.
Result: TROP2 positivity was found in 88 of 120 tumor categories, includ-
ing 73 of 76 epithelial tumor types. Particularly high rates of TROP2
positivity were seen in squamous cell carcinomas of various origins and
various categories of urothelial, breast, prostate, pancreatic, and ovar-
ian cancers (>95% positive). EPCAM positivity was found in 99 of 120
tumor categories, including all 76 epithelial tumor categories. Highest
EPCAM positivity (>95% positive) was seen in small cell lung cancers,
urinary bladder cancers, adenocarcinomas of various organs, and tumors
of the female genital tract. Comparison of TROP2 and EPCAM revealed
co-expression in 84 of 120 tumor types, including 73 of 76 epithelial tumor
categories. Co-expression was most frequent (>95% positive for both
markers) in cancers of the urinary bladder, prostate, pancreas, breast, and
ovary. Exclusive EPCAM positivity was found frequently (>75% EPCAM
positive but TROP2 negative) in various neuroendocrine tumors, testic-
ular cancers, thyroid cancers, and Merkel cell carcinomas. Tumor types
with frequent exclusive expression of TROP2 included of squamous cell
carcinomas of various origins.
Conclusion: TROP2 and EPCAM are abundantly co-expressed in a broad
range of epithelial neoplasms, but exclusively expressed in individual
tumor types. Anti-TROP2 cancer drugs and future anti-EPCAM drugs
may be applicable to a broad range of tumor entities.
Disclosure Statement: e authors declare the following: Antibodies for TROP2
and EPCAM were provided from MS Validated Antibodies GmbH (owned by a
family member of GS).
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts18
Breast Cancer
Best-of-Abstract-Vortrag
114
Outcome of breast cancer patients with low hormone receptor
positivity: Analysis of a 15-year population-based cohort
Simone Schrodi1; Michael Braun2; Anne Andrulat2; Nadia Harbeck3;
SvenMahner4; Marion Kiechle5; Evelyn Klein5; Andreas Schnelzer6;
Christian Schindlbeck4,7; Ingo Bauerfeind8; Gabriele Schubert-Fritschle1;
Valentina Nekljudova9; Doris Mayr10; Wilko Weichert11; Carsten Denkert12;
Sibylle Loibl9,13; Jutta Engel1
1Tumorregister München (TRM), Regionalzentrum München, Bayerisches
Krebsregister, Institut für Medizinische Informationsverarbeitung, Biometrie und
Epidemiologie (IBE), Ludwig-Maximilians Universität, München, Deutschland
2Interdisziplinäres Brustzentrum, Rotkreuzklinikum München, München,
Deutschland
3Frauenklinik der Universität München, Brustzentrum, München, Deutschland
4Frauenklinik der Universität München, München, Deutschland
5Frauenklinik rechts der Isar der Technischen Universität München (TUM),
Brustzentrum, München, Deutschland
6Brustzentrum am RoMed Klinikum Rosenheim, Rosenheim, Deutschland
7Frauenklinik Südostbayern, Brustzentrum, Traunstein, Deutschland
8Frauenklinik am Klinikum Landshut, Brustzentrum, Landshut, Deutschland
9German Breast Group (GBG Forschungs GmbH), Neu-Isenburg, Deutschland
10Pathologisches Institut der Ludwigs-Maximilians-Universität München,
München, Deutschland
11Institut für Pathologie an der Technischen Universität München (TUM),
München, Deutschland
12Institut für Pathologie der Philipps-Universität Marburg (UKGM), Marburg,
Deutschland
13Centrum für Hämatologie und Onkologie Bethanien, Frankfurt, Deutschland
Purpose: Guideline recommendations for treatment of breast cancer with
low hormone receptor (HR) expression (1-9%) are ambiguous and several
studies showed more similarities with HR negative tumors than with HR
strongly positive tumors (≥10%). We used a population-based 15-year
cohort to compare patient characteristics and outcome of HR low positive
tumors with HR negative and HR strongly positive tumors, respectively.
Methods: A total of 38,560 women diagnosed with early invasive breast
cancer between 2004 and 2018 within the scope of the Munich Cancer
Registry (MCR) with 4.9 million inhabitants were included. Descriptive
analyses of prognostic factors, treatment, and outcome-analyses using the
Kaplan-Meier method, cumulative incidence in consideration of com-
peting risks, and multivariate analyses (Cox-regression and Fine-Gray
model) were conducted.
Results: 861 patients (2%) had HR low positive, 4862 (13%) HR negative
and 32,837 (85%) HR strongly positive tumors. Within the HER2 negative
cohort (n=33,366), survival of HR low positive tumors was signicantly
worse than that of HR strongly positive tumors (OS hazard ratio 0.66
[0.55-0.78], whereas between HR low positive and HR negative tumors
no signicant survival dierence could be detected (OS hazard ratio 0.93
[0.78-1.11]). e analyses for time to local recurrence, time to lymph node
recurrence, and time to metastasis showed similar results. In contrast,
within the HER2 positive cohort (n=5194), no statistically signicant dif-
ferences between the three HR groups could be detected in the multivar-
iate analyses. Irrespective of HER2 status, patients with low HR positive
tumors seem not to benet signicantly from endocrine therapy.
Discussion: Current denitions for HR positivity and its clinical rele-
vance should be reconsidered.
Conclusion: Patients with HR low positive/HER2 negative tumors could
be regarded and treated similarly to patients with triple-negative tumors.
Prior presentation: is abstract was also presented at the Senologie
Kongress 2021 and is submitted to a peer reviewed journal.
Disclosure Statement: e authors declare no conict of interest.
Poster
11
Recommendation of the AGO Breast Committee for
HER2-Positive Breast Cancer – Real World Data
onImplementation and Adherence
Wolfgang Janni1; Volkmar Müller2; Jörg Schilling3; Patrik Lindenmaier4;
Andreas Jaeger4
1Universitätsklinikum Ulm - Klinik für Frauenheilkunde und Geburtshilfe, Ulm,
Deutschland
2Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für
Gynäkologie, Hamburg, Deutschland
3Gemeinschaftspraxis Dr. med. Schilling, Dr. med. Till, Dr. med. Kohn, Berlin,
Deutschland
4MMF-Marktforschung GmbH, Dortmund, Deutschland
Background: AGO recommendations reect the standard of care for
diagnostics, therapy and surveillance for both EBC and MBC, and are
updated every year. Our nationwide biennial QA initiative analyzes their
implementation in real-world treatment in Germany.
Methods: We collected data on the care structure of gynecological and
oncological centers (2018: n=309, 2020: n=303). Based on this, data on
diagnosis, current therapy and therapy history of patients with HER2-
positive early (EBC; 2018: n=253, 2020: n=253) and metastatic (MBC;
2018: n=415, 2020: n=451) breast cancer were collected representatively
for all treatment facilities in Germany.
Result: EBC: NACT and antibody therapy with pertuzumab (Pz) and tras-
tuzumab (Tz) (dual HER2 blockade; db) was given in 66% (2018: 58%) of
all patients. Important factors for this are age (RR up to 60 years 1.4 [1.2-
1.6]) and tumor size (RR pT≥2 1.3 [1.1-1.5]). Post-neoadjuvant therapy
with db was 71% (67%) in pN+ and 37% (49%) in pN0. In the adjuvant
setting, the share of db in pN+ was 54% (67%), in pN0 31% (44%). T-DM1
aer NACT was administered in 22%. MBC: 72% (71%) of patients did
not receive HER2 targeted pre-treatment before metastasis. Over all lines
of therapy, patients without HER2 targeted pre-treatment received db with
chemotherapy in 83% (74%), patients with Tz pre-treatment received db
in 59% (53%), and T-DM1 in 25% (27%). Patients with db pre- treatment
received T-DM1 in 80% (73%). In 3rd line of therapy or higher, 85% (73%)
received at least two anti-HER2 therapies prior. Db was given with taxane
mono in 82% (75%), Tz without chemotherapy in 53% (56%).
Discussion: NACT with db is established. e addition of Pz in post-
neoadjuvant and adjuvant settings is only partly triggered by node status.
Anti-HER2 therapy is guided by prior therapies, and the sequence “dual
blockade followed by T-DM1” is established.
Conclusion: National recommendations are promptly implemented into
everyday therapy in Germany. Due to the dynamics of available therapy
options, one should continue to dene and review therapy algorithms
( living guidelines).
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 19
31
Expression of disialoganglioside GD2 in breast cancer
subtypes
Paul Gaß1; Sareetha Kailayangiri2; Hanna Huebner1; Matthias Rübner1;
Arndt Hartmann3; Lothar Häberle1,4; Simon Völkl5; Andreas Mackensen5;
Laura Landgraf3; Rüdiger Schulz-Wendtland6; Nicole Farwick2;
ClaudiaRössig2; Matthias Beckmann1; Peter Andreas Fasching1,7;
RamonaErber3
1Department of Gynecology and Obstetrics, Erlangen University Hospital,
Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University of
ErlangenNuremberg (FAU), Erlangen, Deutschland
2Department of Pediatric Hematology and Oncology, Münster University
Hospital, Münster, Deutschland
3Institute of Pathology, Erlangen University Hospital, Friedrich Alexander
University of ErlangenNuremberg (FAU), Comprehensive Cancer Center
Erlangen-EMN, Erlangen, Deutschland
4Department of Gynecology and Obstetrics, Biostatistics Unit, Erlangen
University Hospital, Friedrich Alex-ander University of ErlangenNuremberg
(FAU), Erlangen, Deutschland
5Department of Internal Medicine 5, Hematology/Oncology, Erlangen University
Hospital, Friedrich Alexander University of ErlangenNuremberg (FAU),
Comprehensive Cancer Center Erlangen-EMN, Erlangen, Deutschland
6Institute of Diagnostic Radiology, Erlangen University Hospital, Comprehensive
Cancer Center Erlangen-EMN, Friedrich Alexander University of Erlangen
Nuremberg (FAU), Erlangen, Deutschland
7Division of Hematology/Oncology, Department of Medicine, David Geen
School of Medicine, Univer-sity of California at Los Angeles, Los Angeles, USA
Background: e disialoganglioside GD2 is a tumor-associated antigen
that may allow targeted immunotherapies (e.g., anti-GD2 antibodies,
GD2 CAR T cells) in patients with neuroblastoma and other solid tumors.
Since GD2 expression has also been reported in subpopulations of breast
cancer patients, this study investigated GD2 expression and its impact on
survival.
Methods: GD2 expression was retrospectively analyzed in a cohort of 894
breast cancer patients, using immunohistochemistry (IHC) and immu-
nouorescence (IF) on tissue microarrays (TMAs). GD2 expression on
IHC (n = 568) and IF (n = 503) was associated with subtypes and patient
outcome.
Result: e highest proportion of GD2-positive tumors was observed
in luminal breast cancer. Signicantly fewer GD2-positive cases were
detected in triple-negative breast cancer (TNBC) compared with other
subtypes. e proportions of GD2-expressing tumors were signicantly
lower in HER2-positive breast cancer in comparison with luminal tumors
on IF staining (but not IHC). GD2 expression on IHC or IF was not sig-
nicantly associated with disease-free or overall survival, either in the
overall cohort or in the individual subtypes.
Discussion: GD2 in breast cancer might be a suitable tumor-associated
antigen that could be targeted on the cell surface in patients with a poor
prognosis according to established clinical and pathological risk factors.
Molecular targeting of pathways associated with GD2 synthesis and
expression would be most eective if GD2 was indeed a marker of aggres-
sive and/or tumor-initiating cells, with critical contributions to tumor
growth and metastasis.
Conclusion: GD2 expression can be found in more than 50 % of breast
cancer tumors, with the highest frequency in hormone receptor–positive
tumors. No correlations between GD2 expression and prognosis were
observed. Patients with GD2-positive advanced breast cancer of all sub-
types may benet from GD2-targeting immunotherapies, which are cur-
rently undergoing clinical testing.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organiser KUKM GmbH and KUKM
can disclose them if needed.
66
Interim analysis (n=150) of the multi-national, prospective,
non-interventional ELEANOR study observing real-life
extended adjuvant treatment with neratinib in patients with
HER2+ / HR+ early breast cancer (eBC)
Diana Lüftner1; Rupert Bartsch2; Urs Breitenstein3; Marija Balic4;
ChristianJackisch5; Volkmar Müller6; Gabriel Rinnerthaler7;
MarcusSchmidt8; Michael Schwitter9; Khalil Zaman10; Denise Wrobel11;
Dagmar Guth12; JürgenTerhaag13; Matthias Zaiss14; Andrea Distelrath15;
Andreas Lorenz16; TimoSchinköthe17; Nadia Harbeck18
1University Hospital Charité, Berlin, Deutschland
2Medical University of Vienna, Department of Medicine I, Division of Oncology,
Vienna, Österreich
3Brust-Zentrum Zürich, Divison of Oncology, Zurich, Schweiz
4Medical University Graz, Department of Internal Medicine, Divison of Oncology,
Graz, Österreich
5Klinikum Oenbach, Department of Gynecology and Obstetrics, Oenbach,
Deutschland
6University Hospital Hamburg-Eppendorf, Department of Gynecology and
Obstetrics, Hamburg, Deutschland
7Paracelsus Medical University, Department of Internal Medicine III with
Haematology, Medical Oncology, Haemostaseology, In-fectiology and
Rheumatology, Oncologic Center, Salzburg Cancer Research Institute
Laboratory for Immunological and Mo-lecular Cancer Research (SCRI-LIMCR),
Salzburg, Österreich
8University Hospital Mainz, Dept. Gynecology, Mainz, Deutschland
9Kantonsspital Graubünden, Chur, Schweiz
10Lausanne University Hospital CHUV, Breast Center, Lausanne, Schweiz
11Sozialstiftung Bamberg Klinikum am Bruderwald, Bamberg, Deutschland
12Gynäko-onkologische Praxis Dr. Guth, Plauen, Deutschland
13Rottal/Inn Clinic, Eggenfelden, Deutschland
14Praxis für interdisziplinaere Onkologie, Freiburg, Deutschland
15Praxisgemeinschaft Onkologie und Urologie, Wilhelmshaven, Deutschland
16Gynäko-onkologische Praxis Dr. Lorenz, Hildburghausen, Deutschland
17CANKADO Service GmbH, Kirchheim, Deutschland
18LMU University Hospital Munich, Breast Center, Dept. OB&GYN, Munich,
Deutschland
Background: Neratinib is registered in Europe as extended adjuvant treat-
ment for adult patients with Human Epidermal Growth Factor Receptor
2-positive (HER2+) and Hormone receptor-positive (HR+) eBC within
one year aer completed adjuvant trastuzumab-based therapy (“EMA-/
Swissmedic-label” population). In the ExteNET trial, extended adjuvant
neratinib improved the absolute 5-year invasive disease-free survival rate
by 5.1% vs. placebo in this population (90.8% vs. 85.7%; HR 0.58 [95%
CI 0.41-0.82])1. In the absence of primary prophylaxis, grade 3 diarrhea
occurred in 39% of patients in the ExteNET trial.1 ELEANOR is the rst
study to investigate real-world use of neratinib and its management in
eBC patients in Germany, Austria and Switzerland.
Methods: 300 patients will be enrolled in accordance with the specica-
tions of the local Summary of Product Characteristics. Primary objective
is adherence to neratinib treatment (i.e., proportion of patients with nera-
tinib intake for ≥75% of treatment days). Secondary objectives include
analysis of prior trastuzumab-based therapies (including pertuzumab and
T-DM1), neratinib dosing and management, relapses, safety / tolerability,
and quality of life (using the CANKADO eHealth application).
Result: Between July 2020 and April 2022, 228 patients were enrolled at 61
sites; patient enrollment is ongoing. We will present baseline demograph-
ics, tumor characteristics, prior treatments and neratinib safety/tolerabil-
ity for the rst 150 enrolled patients (interim analysis, data cut Nov 2021).
Discussion: is analysis presents a snapshot of the current treatment
landscape and real-life neratinib use.
Conclusion: ELEANOR will help to characterize the use of extended adju-
vant HER2-targeted therapy in the current treatment landscape focusing
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts20
on neratinib management aer dierent prior therapies. e study is
funded by Pierre Fabre Pharma GmbH (Freiburg, Germany), Pierre Fabre
Pharma Austria (Wels, Austria) and Pierre Fabre Pharma AG (Allschwil,
Switzerland).
Reference:
1. Chan A et al. Clin Breast Cancer 2021;21(1):80–91.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organiser KUKM GmbH and KUKM
can disclose them if needed.
80
Recommendation of the AGO Breast Committee for
Triple-Negative Breast Cancer – Real World Data
onImplementation and Adherence
Christian Jackisch1; Wolfgang Janni1; Volkmar Müller2; Jörg Schilling3;
Patrik Lindenmaier4; Andreas Jaeger4
1Universitätsklinikum Ulm - Klinik für Frauenheilkunde und Geburtshilfe,
Ulm, Deutschland
2Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für
Gynäkologie, Hamburg, Deutschland
3Gemeinschaftspraxis Dr. med. Schilling, Dr. med. Till, Dr. med. Kohn, Berlin,
Deutschland
4MMF-Marktforschung GmbH, Dortmund, Deutschland
Background: New biomarker-dependent options in therapy for tri-
ple-negative breast cancer (TNBC) are reected in AGO guidelines and
therapy algorithms. Our nationwide biennial QA initiative analyzes their
implementation in real-world treatment in Germany.
Methods: We collected data on the care structure of gynecological and
oncological centers (2018: n=309, 2020: n=303). On this basis, data on
diagnosis, current therapy and therapy history of patients with early
(eTNBC; 2018: n=153, 2020: n=180) and metastatic (mTNBC; 2018:
n=200, 2020: n=205) TNBC were collected representatively for all treat-
ment facilities in Germany.
Result: eTNBC: In 2020, testing for gBRCA mutation was performed in
78% (2018: N/A) of patients up to 60 years of age. NACT was performed
in 86% (78%). A platinum salt was added in 80% (55%) of patients in
the NACT setting and in 65% (32%) in the adjuvant setting. Dose-dense
chemotherapy with anthracycline and taxane was used in 58% (47%) of all
cases. mTNBC: gBRCA testing was performed in 47% (31%) of patients.
PD-L1 expression was measured in 71% (6%) of patients. In PDL1positive
patients, 78% received a PD-L1 inhibitor. In PD-L1 negative patients, 45%
(37%) experienced mono-chemotherapy, 33% (38%) combinations with
VEGFi, and 15% (20%) combinations with platinum. Qualifying patients
received PARPi in 71% (18%).
Discussion: NACT is established, as is the administration of platinum
derivatives and taxanes. Dose-dense regimens are frequently used over
conventional ones, and their importance may increase. In mTNBC,
PD-L1 testing is performed in the majority of patients, while BRCA test-
ing is performed in only half. Immunotherapy and PARP inhibition are
the preferred options in qualifying patients. For the majority of mTNBC
patients, however, treatment options remain unchanged.
Conclusion: AGO recommendations for biomarker testing are promptly
implemented into everyday therapy in Germany. Due to the dynamics of
the available therapy options, one should continue to dene and review
quality indicators.
Disclosure Statement: e authors declare no conict of interest.
120
Knockdown of AKT3 activates HER2 and DDR kinases in
bone-seeking breast cancer cells, promotes metastasis
in vivo and attenuates the TGF/CTGF Axis
Nico Hinz1; Anke Baranowsky2; Michael Horn3; Malte Kriegs4;
FreyaSibbertsen1; Daniel Smit1; Philippe Clezardin5; Tobias Lange6;
Thorsten Schinke2; Manfred Jücker1
1Institute of Biochemistry and Signal Transduction, University Medical Center
Hamburg Eppendorf, Hamburg, Deutschland
2Department of Osteology and Biomechanics, University Medical Center
Hamburg Eppendorf, Hamburg, Deutschland
3University Cancer Center Hamburg, University Medical Center Hamburg
Eppendorf, Hamburg, Deutschland
4Department of Radiotherapy & Radiation Oncology, University Medical Center
Hamburg Eppendorf, Hamburg, Deutschland
5Research Unit UMR S1033, INSERM, Lyon, Frankreich
6Department of Anatomy and Experimental Morphology, University Medical
Center Hamburg Eppendorf, Hamburg, Deutschland
Background: Bone metastases frequently occur in breast cancer patients
and lack appropriate treatment options. Understanding the molecu-
lar mechanisms involved in the multistep process of breast cancer bone
metastasis and tumor-induced osteolysis is of paramount interest. e
serine/threonine kinase AKT plays a crucial role in breast cancer bone
metastasis but the eect of individual AKT isoforms remains unclear.
Methods: AKT isoform-specic knockdowns were generated in the
bone-seeking MDA-MB-231 BO subline and the eect on proliferation,
migration, invasion, and chemotaxis was analyzed by live-cell imaging.
Kinome proling and Western blot analysis of the TGF/CTGF axis were
conducted and metastasis was evaluated by intracardiac inoculation of
tumor cells into NOD scid gamma (NSG) mice.
Result: MDA-MB-231 BO cells exhibited an elevated AKT3 kinase
activity in vitro and responded to combined treatment with AKT- and
mTOR-inhibitors. Knockdown of AKT3 signicantly increased migra-
tion, invasion, and chemotaxis in vitro and metastasis to bone but did
not signicantly enhance osteolysis. Furthermore, knockdown of AKT3
increased the activity of pro-metastatic HER2 and DDR1/2 but low-
ered protein levels of CTGF aer TGF-stimulation, an axis involved in
tumor-induced osteolysis.
Discussion: Our data indicate that the three AKT isoforms are dieren-
tially involved in the regulation of breast cancer metastasis. We demon-
strate that knockdown of AKT3 in MDA-MB-231 BO cells resulted in an
enhanced metastasis to the bone in NSG mice. In addition, we demon-
strate that the combined treatment with AKT and mTOR inhibitors syner-
gistically inhibited proliferation and migration of MDA-MB-231 BO cells.
Conclusion: We demonstrate that knockdown of AKT3 in bone-seeking
breast cancer cells promotes metastasis to the bone. On the basis of our
data, the treatment of triple negative breast cancer in a non-metastatic
stage with an AKT1/2 inhibitor in combination with mTOR inhibitors
should be analyzed in further studies.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 21
127
Process evaluation of an intensied patient-reported outcome
monitoring study with metastatic breast cancer patients
Clara Breidenbach1; Christoph Kowalski1; Anna Maria Hage2;
TheresePross2; Friedrich Kühn2; Maria Margarete Karsten2
1Deutsche Krebsgesellschaft e. V., Berlin, Deutschland
2Charité Universitaetsmedizin Berlin, Department of Gynecology,
Berlin,Deutschland
Background: Treating metastatic breast cancer patients represents a chal-
lenge from a medical, psychosocial and economical point of view for the
entire clinical team. Earlier research has shown that an intensied mon-
itoring with patient-reported outcomes (PROs) can improve metastatic
cancer patients’ quality of live and survival. e aim of the randomized
multicentric PRO B study is to investigate if those positive eects are
also applicable to metastatic breast cancer patients in the German health
care system. In case of positive results, the PRO monitoring should be
transferred to routine care. erefore, an integrated process evaluation is
planned during the study. It aims to answer whether the intervention is
feasible in everyday clinical practice as well as whether implementation is
center (“context”) dependent.
Methods: Online surveys with all study sites will be conducted at several
time points during the intervention phase of the study (May 2021 – May
2023) to generate a general overview of the acceptance, satisfaction and
outreach of the intervention among health professionals. Furthermore,
semi-structured interviews with health professionals from high perform-
ing (with regard to recruitment) as well as from lower performing study
sites will be performed at several time points to gain a deeper understand-
ing of barriers and facilitators for intervention adherence. e interview
guide will be inspired by the Normalisation Process eory.
Result: First results will be available at the time of the congress.
Discussion: e process evaluation embedded in the PRO B study may
help to assess the feasibility, acceptance and quality of the intervention
and thus provide insights for its implementation. In addition, process
evaluation can be used to identify causal mechanisms and how context
inuences the results of the intervention study.
Conclusion: Process evaluation will provide recommendations for the
implementation of intensied PRO monitoring in breast cancer centers
in Germany.
Disclosure Statement: e authors declare the following: Clara Breidenbach and
Christoph Kowalski are employees of the German Cancer Society, one of the two
bodies responsible for the certication of breast cancer centers.
157
Association between mammographic breast density and
achievement of a pathologic complete remission (pCR)
after neoadjuvant chemotherapy (NACT) for early breast
cancer (EBC)
Mohamed Shaheen1; Cornelia Kolberg-Liedtke2; Oliver Homann2;
Ann-Kathrin Bittner2; Sarah Wetzig3; Miltiades Stephanou1;
Hans-Christian Kolberg1
1Marienhospital Bottrop, Klinik für Gynäkologie und Geburtshilfe, Bottrop,
Deutschland
2Universitätsklinikum Essen, Klinik für Frauenheilkunde und Geburtshilfe, Essen,
Deutschland
3Marienkrankenhaus Schwerte, Brustzentrum, Schwerte, Deutschland
Background: Achievement of pathologic complete remission (pCR) aer
NACT is indicating an improved prognosis. An association between pCR
and mammographic breast density as dened by BIRADS (Breast Imaging
Reporting and Data System) could be demonstrated. However, the de-
nition of mammographic breast density by the American College of
Radiology (ACR) is widely used worldwide and data regarding an associ-
ation of breast density by this denition and pCR aer NACT are missing.
Methods: We conducted a retrospective analysis among patients who had
received neoadjuvant chemotherapy (NACT) for EBC. An association
between mammographic breast density (ACR) and pCR was analyzed.
Result: 185 patients were included in this analysis, 35.7% of whom
achieved a pCR. Mammographic breast density was ACR 1 in 15.1%, ACR
2 in 41.6%, ACR3 in 38.4% and ACR 4 in 4.9% of the patients. A negative
correlation between mammographic breast density and pCR (correlation
coecient (CC) -0.240)(p=0.001) and the association of decreasing pCR
rates with increasing mammographic breast density (pCR rates by ACR 1:
53.6%, ACR 2: 41.6%, ACR 3: 25.4% and ACR 4: 11.1 %)(p=0.013) were
statistically signicant. ese results were independent of age, ER status,
PR status, HER2neu status and grading.
Conclusion: In our retrospective analysis higher mammographic breast
density as dened by ACR was signicantly correlated with a lower chance
of achieving a pCR aer NACT. e pathophysiological cause of this asso-
ciation should be further investigated to reveal potential mechanisms of
treatment resistance.
Disclosure Statement: e authors declare no conict of interest.
161
Benets and risks of patient participation in multidisciplinary
tumor conferences in breast cancer: main ndings of the
mixed methods PINTU study
Lena Ansmann1; Christian Heuser2; Annika Diekmann2;
BarbaraSchellenberger2; Nicole Ernstmann2
1Abteilung für Organisationsbezogene Versorgungsforschung, University of
Oldenburg, School of Medicine and Health Sciences, Oldenburg, Deutschland
2Forschungsstelle für Gesundheitskommunikation und Versorgungsforschung,
Klinik und Poliklinik für Psychosomatische Medizin und Psychotherapie,
Universitätsklinikum Bonn, Bonn, Deutschland
Background: Research in breast cancer centers in Germany revealed that
between 5-7% of patients have participated in multidisciplinary tumor
conferences (MTCs) during their own case discussion. Research on the
risks and benets is rare. e PINTU study aimed to answer the follow-
ing research questions: How do providers perceive patient participation
in MTCs with regard to feasibility and quality of decision-making? In
how far do MTCs with and without patient participation dier? How do
patients experience participation and how does it aect PROs?
Methods: In an exploratory, observational, prospective multicenter study,
MTCs with/without patient participation in 6 breast and gynecological
cancer centers in NRW were examined. First, n=32 interviews with pro-
viders were carried out. Second, video/audiotaped observations in MTCs
were conducted (n=317, n=95 patients with and n=222 without partici-
pation). ird, patients with/without participation were surveyed before
(T0), directly aer MTC (T1) and 4 weeks aer MTC (T2). Survey data
were analyzed by descriptive and multivariate statistics using propensity
scores.
Result: (1) e way patient participation is implemented varied strongly
by center. (2) Case discussions with patients present may not be feasible in
routine care. (3) Most patients experienced patient participation in MTC
as positive, whereas some reported negative experiences. (4) Providers
reported a mixed picture of positive and negative experiences as well. (5)
Shared decision making in MTCs seemed dicult under the current cir-
cumstances. (6) e development of fear of cancer progression, unmet
information needs and quality of life did not show substantial dierences
by MTC participation.
Discussion: Although numbers of patients and centers are limited, this is
the largest study to date on this controversial topic.
Conclusion: e next urgent questions to be answered before recom-
mendations for or against patient participation in MTCs can be made are:
Which patients could benet? How can MTC participation be arranged
for the patients benet?
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts22
186
Reduction of the ablation rate through oncoplastic surgery
in breast-conserving therapy for breast cancer -Experience
of a singular breast center
Hala Allakeh; Wladimir Pauker
Rotenburg (Wümme), AGAPLESION Diakonieklinikum Rotenburg, Frauenklinik,
Rotenburg (Wümme), Deutschland
Objective: In cases of an unfavorable relative tumor size or an unfavor-
able tumor location as well as multicentricity and multifocality of a breast
cancer, an oncologically safe excision with a cosmetic result can be carried
out by an oncoplastic operation and the rate of mastectomies can be sig-
nicantly reduced.
Maternal: From December 2019 to July 2021, 273 patients with a pri-
marily histologically conrmed breast cancer were treated surgically, 97
(37.5%) of them with the use of oncoplastic breast reduction techniques.
29 (10.6%) of 273 patients received ablatio mammae or skin sparing mas-
tectomy (SSM) either primarily or as a result of the tumor-involved mar-
gins aer tumor removal. Four categories of breast-conserving operations
were performed: conventional tumorectomy, segment resection with mas-
topexy was ideal for tumors in the upper and lower outer quadrants. A
modied Burow’s triangle advancement ap was used for tumors in the
upper and lower inner quadrants. A round-block reduction technique was
performed for periareolar lesions. For subareolar tumors, the Grisotti ap
technique was used.
Results: e mastectomy rate in retrospective data from 748 patients was
21.6% (162) compared to 10.6% (29) from 273 patients with 37.5% (97)
use of oncoplastic breast reduction techniques.
Discussion: e use of oncoplastic technology in modern senology can
signicantly reduce the mastectomy rate.
To summarize: e oncoplastic breast reduction techniques enable large-
scale excisions to be carried out with good oncological safety as well as
deliver positive cosmetic results and can be used as an alternative to mas-
tectomy in large carcinomas. ere is very limited evidence of oncological
outcomes of breast-conserving surgery for these large tumors.
Disclosure Statement: e authors declare no conict of interest.
190
Heterogeneity between core needle biopsy and primary
tumor tissue in early breast cancer patients: Comparison of
intrinsic subtypes after dierent treatment regimes
Laura Weydandt1; Anne Kreklau1; Ivonne Nel1; Lars-Christian Horn2;
Bahriye Aktas1
1Universitätsklinikum Leipzig, Klinik und Poliklinik für Frauenheilkunde,
Leipzig, Deutschland
2Universitätsklinikum Leipzig, Institut für Pathologie, Leipzig, Deutschland
Background: All initial therapeutic decisions in early breast cancer are
commonly based on the expression proles of estrogen (ER), progesterone
(PR) and the human epidermal growth factor 2 (HER2) receptors. Only
little data is known about receptor changes aer upfront therapy. Here, we
compared receptor expression proles between core needle biopsy (CNB)
tissue and primary tumor tissue aer dierent treatment regimes.
Methods: In a German single center study, we retrospectively analyzed
248 breast cancer patients during primary treatment regime between 2014
and 2020. Patients had either neoadjuvant chemotherapy, neoadjuvant
endocrine therapy or no upfront therapy. Tumor material was obtained
by core needle biopsy (CNB) at primary diagnosis and during primary
oncological surgery of the axilla and breast. Analysis of histological sub-
type, grading, Ki67 index and expression proling of ER, PR, HER2, was
performed using formalin-xed, paran-embedded (FFPE) specimens.
Tumors were grouped into dierent intrinsic subtypes according to the
international St. Gallen classication in either Luminal A, Luminal B,
HER2-enriched or triple negative.
Result: Overall, 77 (36%) patients had an intrinsic subtype change
between CNB and denitive surgical treatment, 139 (64 %) patients had
no subtype change. ere were 44 (52%) changes aer neoadjuvant che-
motherapy, 17 (35%) changes aer neoadjuvant endocrine therapy and 16
(20%) subtype changes aer no upfront therapy (p<0.0001 for the eect of
neoadjuvant chemotherapy).
Discussion: Our results imply the high frequency of intrinsic subtype
changes aer neoadjuvant therapy. Subtype changes should be taken into
account for an optimal and individual treatment.
Conclusion: Further research needs to be conducted to investigate
whether an individual treatment decision based on the receptor prole
aer primary treatment might improve clinical outcome of breast cancer
patients.
Disclosure Statement: e authors declare no conict of interest.
210
An open-label, multinational, multicenter, phase 3b/4 study
of trastuzumab deruxtecan (T-DXd) in patients with or without
baseline brain metastasis with previously treated advanced/
metastatic human epidermal growth factor receptor
2-positive breast cancer (HER2+ BC): DESTINY-Breast12
Volkmar Müller1; Nancy U. Lin2; Eva Ciruelos3; Guy Jerusalem4;
Naoki Niikura5; Giuseppe Viale6; Emma Oscroft7; Shawn Anand7;
Graham Walker7; Nadia Harbeck8
1University Medical Center Hamburg-Eppendorf, Hamburg, Deutschland
2Dana-Farber Cancer Institute, Boston, USA
3University Hospital 12 de Octubre, Madrid, Spanien
4Centre Hospitalier Universitaire du Sart Tilman Liège and Liège University,
Liège, Belgien
5Tokai University School of Medicine, Kanagawa, Japan
6European Institute of Oncology, Milan, Italien
7AstraZeneca Pharmaceuticals, Gaithersburg, USA
8Breast Center, LMU University Hospital, Munich, Deutschland
Background: HER2+ BC is associated with a high incidence (up to 50%)
of brain metastasis (BM) despite advances in treatment [1]. Although
several agents have been studied in patients (pts) with HER2+ BC with
BM, an unmet need remains due to the poor prognosis in these pts. In
DESTINY-Breast01, T-DXd demonstrated ecacy in the overall popula-
tion and preliminary ecacy in a subgroup of pts with stable BM, with
an objective response rate (ORR) of 61.4% and an extracranial conrmed
ORR by independent central review (ICR) of 58.3%, median progres-
sion-free survival (PFS) of 19.4 mo and 18.1 mo, and median duration
of response (DOR) of 20.8 mo and 16.9 mo, respectively[2, 3]. Here we
describe a trial evaluating T-DXd in pts ± BM with previously treated
advanced/metastatic HER2+ BC.
Methods: DESTINY-Breast12 (NCT04739761) is an open-label, multi-
center, international, phase 3b/4 study assessing the ecacy and safety of
T-DXd 5.4 mg/kg in pts with HER2+ BC ± BM. Pts will be enrolled in 1
of 2 cohorts (250 pts each): cohort 1 (without BM at baseline) and cohort
2 (with BM at baseline). Pts must have previously treated advanced/meta-
static HER2+ BC that has progressed with ≥1 prior anti-HER2–based reg-
imen and received ≤2 lines of therapy in the metastatic setting (excludes
pts with prior tucatinib treatment). Pts with BM must have untreated
BM not needing immediate local therapy or previously treated stable
or progressing BM. Primary endpoints are ORR in cohort 1 and PFS in
cohort 2 (both by RECIST version 1.1 per ICR). Secondary endpoints in
both cohorts are OS, DOR, time to progression, duration of subsequent
therapy, PFS2, safety, and changes in symptoms, functioning, and QOL.
Incidence of new symptomatic BM is a secondary endpoint in cohort 1,
and ORR and CNS ORR by RECIST 1.1 per ICR, CNS PFS and DOR, and
time to new BM are secondary endpoints in cohort 2.
Result: n/a
Discussion: n/a
Conclusion: n/a
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 23
Indication of source:
1. Freedman, R.A., et al. 2019. 37(13): p. 1081-1089.
2. Modi, S., et al. 2021. 81(4 Supplement): p. PD3-06-PD3-06.
3. Jerusalem, G., et al. Annals of Oncology, 2020. 31: p. S63-S64.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
246
Implementation of new tests and treatments for patients
with advanced triple negative breast cancer in routine
care – data from the registry platform OPAL
Mark-Oliver Zahn1; Anja Welt2; Marc Thill3; Elmar Stickeler4;
Matthias Zaiss5; Arnd Nusch6; Erik Engel7; Marco Chiabudini8;
Lisa Kruggel8; Martina Jänicke8; Norbert Marschner5; Achim Wöckel9;
Nadia Harbeck10; Thomas Decker11
1Überörtliche Berufsausübungsgemeinschaft MVZ Onkologische Kooperation
Harz, Goslar, Deutschland
2Universitätsklinikum Essen Innere Klinik Tumorforschung, Essen, Deutschland
3Agaplesion Markus Krankenhaus Klinik für Gynäkologie und Gynäkologische
Onkologie, Frankfurt a.M., Deutschland
4Uniklinik RWTH Aachen, Gynäkologie und Geburtsmedizin, Aachen,
Deutschland
5Praxis für interdisziplinäre Onkologie & Hämatologie, Freiburg i.Br., Deutschland
6Praxis für Hämatologie und internistische Onkologie, Ratingen, Deutschland
7Hämatologisch-Onkologische Praxis Altona (HOPA), Hamburg, Deutschland
8iOMEDICO, Freiburg i.Br., Deutschland
9Universitätsklinikum Würzburg Frauenklinik und Poliklinik, Würzburg,
Deutschland
10LMU Klinikum München, Brustzentrum, Frauenklinik, München, Deutschland
11Studienzentrum Onkologie Ravensburg Prof. Dr. Dechow, Prof. Dr. Decker,
Dr.Nonnenbroich GbR, Ravensburg, Deutschland
Background: Since 2019, new treatment options for patients (pts) with
advanced triple negative breast cancer (TNBC) have been approved in the
EU: PARP inhibitors for pts with BRCA-mutated and PD-L1 inhibitors
for pts with PD-L1 positive BC. e OPAL registry platform was used to
analyze the implementation of these new tests and treatments into routine
care.
Methods: OPAL (NCT03417115) is a prospective registry that continues
the Tumor Registry Breast Cancer. By March 2022, a total of 3883 pts
with advanced BC had been recruited, of whom 1883 since start of OPAL
(01/2018). Details on all (sequential) treatments, patient and tumor char-
acteristics, biomarker testing, and outcomes are collected. Here data were
analyzed for 254 OPAL pts with TNBC.
Result: Overall, most frequent rst-line regimens since 2018 were (nab)
paclitaxel ±bevacizumab (BEV) (23%), (nab)paclitaxel +atezolizumab
(21%), capecitabine ±BEV (19%), (nab)paclitaxel +carboplatin ±BEV
(10%) and carboplatin +gemcitabine (4%). Second-line (n=98), most
frequent treatments were anthracyclines (18%) and eribulin (17%). Since
2018, the PD-L1 testing rate at start of rst-line treatment has increased
from 14% to 74%. Out of 133 pts tested, 63 pts (47%) had a positive test
result, 53 since the approval of checkpoint-inhibitor atezolizumab (ATZ)
in 08/2019. 41 out of 53 pts (77%) were treated with ATZ rst-line. e
testing rate for BRCA1 or BRCA2 mutations was between 9-14%. Out of
30 pts tested, 3 pts carried a mutation, but no use of PARP-inhibitors was
documented so far in rst-line. Prior to approval of ATZ, median PFS and
OS was 6.4 months (95% CI 5.4-7.3) and 14.9 months (95% CI 12.3-18.4),
respectively. Aer approval of ATZ, the majority of all TNBC pts were still
alive. Updated data will be presented.
Conclusion: Our data show that PD-L1 testing and the new treatment
option for PD-L1 positive tumors were quickly implemented in routine
care. BRCA1/2 testing is performed less oen, especially in rst-line sit-
uation. With longer follow-up, OPAL will show the impact of these new
targeted therapies on the outcome in routine care.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
269
AXSANA – EUBREAST 3 (AXillary Surgery After NeoAdjuvant
Treatment): An international prospective multicenter cohort
study of the EUBREAST study group to evaluate dierent
surgical methods of axillary staging (sentinel lymph node
biopsy, targeted axillary dissection, axillary dissection) in
clinically node-positive breast cancer patients treated with
neoadjuvant chemotherapy (NCT04373655)
Maggie Banys-Paluchowski1,2; Ste Hartmann3; Elmar Stickeler4;
Jana de Boniface5,6; Oreste Gentilini7; Sarah Fröhlich3; Marc Thill8;
Franziska Ruf1; Michael Hauptmann9; Güldeniz Karadeniz Cakmak10;
Isabel Teresa Rubio11; Maria Luisa Gasparri12,13; Michalis Kontos14;
Eduard-Alexandru Bonci15,16; Laura Niinikoski17; Rosa DI Micco7;
Dawid Murawa18; David Pinto19; Florentia Peintinger20,21; Lukas Dostalek22;
Christine Solbach23; Matilda Appelgren5; Jens-Uwe Blohmer24;
Elisabeth Thiemann25; Michael Weigel26; Gabriele Kaltenecker27; Kerstin
Ramaker28; Michael G. Schrauder29; Thorsten Kühn30
1Department of Obstetrics and Gynecology, University Hospital of Schleswig
Holstein, Campus Lübeck, Lübeck, Deutschland
2Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf,
Deutschland
3University Hospital Rostock, Department of Gynecology and Obstetrics,
Rostock, Deutschland
4University Hospital Aachen, Department of Gynecology and Obstetrics, Aachen,
Deutschland
5Karolinska Institutet, Dept. of Molecular Medicine and Surgery, Stockholm,
Schweden
6Capio St. Görans Hospital, Dept. of Surgery, Stockholm, Schweden
7San Raaele Hospital Milan, Milano, Italien
8AGAPLESION Markus Krankenhaus, Department of Gynecology and
Gynecological Oncology, Frankfurt am Main, Deutschland
9Brandenburg Medical School Theodor Fontane, Neuruppin, Deutschland
10Zonguldak BEUN The School of Medicine, General Surgery Department, Breast
and Endocrine Unit, Kozlu/Zonguldak, Türkei
11Breast Surgical Unit, Clínica Universidad de Navarra, Madrid, Spanien
12Department of Gynecology and Obstetrics, Ente Ospedaliero Cantonale,
Ospedale Regionale di Lugano, Lugano, Schweiz
13University of the Italian Switzerland (USI), Faculty of Biomedicine, Lugano,
Schweiz
141st Department of Surgery, Laiko Hospital, National and Kapodistrian
University of Athens, Athens, Griechenland
15Department of Surgical Oncology, ”Prof. Dr. Ion ChiricuțăInstitute of
Oncology, Cluj-Napoca, Rumänien
1611th Department of Oncological Surgery and Gynecological Oncology, “Iuliu
HațieganuUniversity of Medicine and Pharmacy, Cluj-Napoca, Rumänien
17Breast Surgery Unit, Comprehensive Cancer Center, Helsinki University
Hospital, University of Helsinki, Finnland
18Department of General Surgery and Surgical Oncology, Collegium Medicum,
University of Zielona Góra, Zielona ra, Polen
19Breast Unit, Champalimaud Clinical Center, Champalimaud Foundation,
Lisboa, Portugal
20Institute of Pathology, Medical Univ. Graz, Graz, Österreich
21Department of Gynecology, LKH Leoben, Leoben, Österreich
22Gynecologic Oncology Center, Department of Obstetrics and Gynecology,
First Faculty of Medicine, Charles University, General University Hospital, Prague,
Tschechische Republik
23Breast Center, Department of Gynecology and Obstetrics, University of
Frankfurt, Frankfurt, Deutschland
24Department of Gynecology and Breast Cancer Center, Charité Berlin, Berlin,
Deutschland
25Brustzentrum Osnabrück - Niels-Stensen-Kliniken, Osnabrück, Deutschland
26Leopoldina-Krankenhaus, Schweinfurt, Deutschland
27Städtisches Klinikum Karlsruhe Frauenklinik, Karlsruhe, Deutschland
28Regio Klinikum Pinneberg, Pinneberg, Deutschland
29Klinikum Aschaenburg-Alzenau, Aschaenburg, Deutschland
30Department of Gynecology and Obstetrics, Klinikum Esslingen, Esslingen,
Deutschland
Background: e optimal surgical staging procedure of the axilla in
patients who convert from a clinically positive to a clinically negative node
status through neoadjuvant chemotherapy is still controversial. Widely
diverse techniques such as Axillary Lymph Node Dissection (ALND),
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts24
Targeted Axillary Dissection (TAD), Targeted Lymph Node Biopsy
(TLNB) and Sentinel Lymph Node Biopsy alone (SLNB) are given pref-
erence in dierent international guidelines. So far, no comparative data
on the oncological outcome or the morbidity of the dierent procedures
are available.
Methods: AXSANA is an international prospective cohort study includ-
ing cN+ patients treated with dierent axillary staging techniques. e
study was initiated by the EUBREAST network and funded by AGO-B,
Claudia von Schilling Foundation, Ehmann-Stiung Savognin, AWOgyn,
EndoMag, MeritMedical and Mammotome, and supported by NOGGO
and GBG. Primary aims are invasive disease-free survival, axillary recur-
rence rate and quality of life in cN+ → ycN0 patients treated with dierent
staging techniques. Target accrual is 3000 patients.
Result: So far, 868 cN+ patients from 13 countries were recruited. Median
age was 52 years. Nodes were suspicious upon clinical examination and
imaging in 67% and imaging only in 33% of patients. 24% of patients had
≥4 suspicious lymph nodes. In 58% of cases, ≥1 target node was marked
(1 node in 90%, 2 nodes in 8%, ≥3 nodes in 2%). Clip/coil was used in
79% of patients, followed by carbon ink (12%) and magnetic seed (9%).
70% of patients converted to ycN0. TAD was planned in 43%, ALND in
38%, SLNB in 15% and TLNB in 7% of patients. 61% of study sites choos-
ing TAD reported to have performed ≥30 procedures. Among patients
receiving preoperative target node localization, most (75%) underwent
wire-guided localization.
Discussion: Our preliminary data show that axillary staging is very het-
erogeneous among countries. TAD is widely used despite lack of long-
term oncological data.
Conclusion: Final results of AXSANA will contribute to clarify the onco-
logical safety of axillary surgical de-escalation.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
283
persevERA Breast Cancer (BC): Phase III study evaluating
the ecacy and safety of giredestrant (GDC-9545) +
palbociclib versus letrozole + palbociclib in patients (pts)
with estrogen-receptor-positive, HER2-negative locally
advanced or metastatic BC (ER+/HER2– LA/mBC)
Volkmar Müller1; Nicholas Turner2; Komal Jhaveri3; Aditya Bardia4;
Naoki Niikura5; Véronique Diéras6; Carlos Barrios7; Seock-Ah Im8;
Meritxell Bellet9; Ching-Wei Chang10; Graham Ross11; Monika Patre11;
Sherene Loi12
1Universitätsklinikum Hamburg Eppendorf, Klinik und Poliklinik für Gynäkologie,
Hamburg, Deutschland
2The Royal Marsden Hospital, London, Vereinigtes Königreich
3Memorial Sloan-Kettering Cancer Center, New York, USA
4Mass General Cancer Center, Boston, USA
5Tōkai-Universität, Shibuya City, Japan
6Eugene Marquis Center, Rennes, Frankreich
7Centro de Pesquisa em Oncologia, Porto Alegre, Brasilien
8Seoul National University College of Medicine, Seoul, Republik Korea
9Hospital Universitari Vall dHebron, Barcelona, Spanien
10Genentech Inc, South San Francisco, USA
11Homann-La Roche, Basel, Schweiz
12Peter MacCallum Cancer Centre, Melbourne, Australien
Background: Modulating estrogen synthesis and/or ER activity is the
mainstay of treatment for pts with ER+ BC. Despite substantial progress,
many pts experience relapse during/aer adjuvant endocrine therapy.
However, even though resistant to aromatase inhibitors (AIs) or tamox-
ifen, growth and survival of the majority of tumors are thought to remain
dependent on ER signaling. erapeutic resistance can arise from muta-
tions in ESR1, which can drive estrogen-independent transcription and
proliferation. e highly potent, non-steroidal oral selective ER degrader
giredestrant achieves robust ER occupancy and is active regardless
of ESR1 mutation status. Phase I data indicate that giredestrant is well
tolerated, with encouraging activity as a single agent and in combination
with the CDK4/6 inhibitor palbociclib.
Methods: persevERA BC (NCT04546009) is a double-blind, placebo-
controlled, randomized, multicenter phase III study designed to evaluate
the ecacy and safety of 1L giredestrant + palbociclib in pts with ER+/
HER2– LA/mBC. Randomization: 1:1 to either giredestrant (30 mg PO)
plus letrozole placebo QD or letrozole (2.5 mg PO) plus giredestrant pla-
cebo QD on Days 1–28 of each 28-day cycle, with palbociclib (125 mg PO
QD) on Days 1–21 of each 28-day cycle. Men and premenopausal women
will receive an LHRH agonist. Eligibility: females or males ≥18 years old
with measurable disease or evaluable bone disease and no prior treat-
ment for advanced disease. Pts who received prior fulvestrant, who have
relapsed within 12 months of completion of (neo)adjuvant therapy with
an AI and/or prior therapy with CDK4/6 inhibitor are not eligible; relapse
during tamoxifen therapy but >24 months aer the start of tamoxifen
therapy is allowed. Stratication: site of disease, disease-free interval since
the end of (neo)adjuvant therapy, menopausal status, geographic region.
progression-free survival. Secondary endpoints include overall survival,
objective response rate, duration of response, clinical benet rate, QoL
and safety. Enrollment is open; target recruitment is 978 pts.
Disclosure Statement: e authors declare no conict of interest.
306
Current treatment landscape of advanced triple negative
breast cancer patients among a network of oce-based
oncologists and gynecologists in Germany
Michael Braun1,2; Oliver J. Stoetzer3; Christoph Salat3; Jens Borchardt4;
Ralf Reichelt4; Andra Kuske5
1Brustzentrum Rotkreuzklinikum München, München, Deutschland
2MVZ für Senologie, Gyn. Onkologie und Spezielle Operative Gynäkologie,
München, Deutschland
3Medizinisches Zentrum für Hämatologie und Onkologie München, München,
Deutschland
4Onkotrakt AG, Hamburg, Deutschland
5Gilead Sciences GmbH, Martinsried, Deutschland
Background: Despite new developments in treatment landscape of
advanced triple negative breast cancer (mTNBC) prognosis remains poor.
Real world data on patients (pts) outside of clinical trials are rare but very
helpful to understand and improve the standard of care.
Methods: Data was collected from 48 oce-based oncologists and gyne-
cologists in Germany (DE) using oncotrace soware. Jan 2014 - Jun 2021,
7533 breast cancer (BC) pts were documented within the Onkotrakt net-
work. For descriptive statistical evaluation SPSS soware was used.
Result: BC subtypes in palliative (m) setting are distributed as follows:
1619 (64%) HER2-/HR+, 195 (8%) HER2+/HR-, 377 (15%) HER2+/HR+,
360 (14%) TNBC. Top 5 therapy regimen in 1 line (L) m setting for TNBC
(n=248): 33% taxane (+bevacizumab (bev) 48%), 21% carboplatin + che-
motherapy (carbo + CTx) (+ bev 20%), 13% capecitabine (cap) (+ bev
75%), 8% atezolizumab + nab-Paclitaxel (atezo + nab-P), 5% vinorelbin
(vino). Top 5 therapies in ≥2L (n=372): 17% eribulin, 16% carbo + CTx (+
beva 10%), 12% taxane (+ beva 34%), 12% anthracycline (+ beva 6%), 11%
vino. Median duration of 1L top 5 therapies was 91 d taxane, 112 d carbo +
CTx, 140 d cap, 154 d atezo + nab-P and 85 d vino. Median duration of 2L
top 5 therapies was 126 d taxane, 88 d carbo+CTx 76 d cap, 113 d eribulin,
77 d vino. In ≥3L duration of treatment decreased.
Discussion: Combination of taxane, cap or platinum with beva for
mTNBC is very common in DE. Atezo + nab-P approved in 2019 gained
importance in 1L m setting while eribulin is the most common therapy in
≥2L. Duration of 1L and ≥2L therapy conrmed the diculty in treating
mTNBC pts.
Conclusion: Here, we describe the treatment reality for mTNBC pts in a
network of oce-based oncologists and gynecologists in DE. Pts receive
various CTx options but only a few targeted therapies. Since 2019 PD-L1
inhibitors (i) for PD-L1-positive tumors as well as PARPi for pts with
BRCA germline mutations become more important. Recent study data on
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 25
antibody-drug-conjugates e.g. Sacituzumab Govitecan may provide novel
treatment options for mTNBC pts.
Disclosure Statement: e authors declare the following: Funding: Gilead
Sciences GmbH
309
Impact of Tucatinib on Progression Free Survival in Patients
with HER2 + Metastatic Breast Cancer and Brain Metastases
Sibylle Loibl1; Nancy Lin2; Rashmi K. Murthy3; Sara A. Hurvitz4;
Virginia Borges5; Mafalda Oliveria6; Catherine Oakman7; Sarah Khan8;
Cynthia Lynch9; Kelly Westbrook10; Catherine Doyle11; Mattea Reinisch12;
Marco Callenoni13; Dennis Slamon4; Gabriel Hortobagyi3; Eric Winer2;
Jorge Ramos14; Wentao Feng15; Thomas Bachelot16
1GBG Forschungs GmbH, Neu-Isenburg, Deutschland
2Dana Farber Cancer Institute, Boston, USA
3MD Anderson Cancer Center, University of Texas, Houston, USA
4UCLA Medical Center, Jonsson Comprehensive Cancer Center, Los Angeles, USA
5University of Colorado Cancer Center, Aurora, USA
6Hospital Universitario Vall DHebron, Barcelona, Spanien
7Sunshine Hospital, St. Albans, Australien
8Nottingham University Hospitals NHS Trust, Department of Oncology,
Nottingham, Vereinigtes Königreich
9Cancer Treatment Centers of America, Western Regional Medical Center,
Goodyear, USA
10Duke University Medical Center, Durham, USA
11Hopital du Saint-Sacrement, CHU de Quebec-Universite Laval, Quebec, Kanada
12Kliniken Essen-Mitte - Evang. Huyssens-Stiftung, Essen, Deutschland
13Istituto Europeo di Oncologia, Milano, Italien
14Seagen Inc., Clinical Development, Bothell, USA
15Seagen Inc., Biostatistics, Bothell, USA
16Centre Léon Bérard, Lyon, Frankreich
Tucatinib (TUC) is an oral tyrosine kinase inhibitor highly specic for
HER2. TUC is approved in multiple regions for use in combination with
trastuzumab (T) and capecitabine (C) in adult patients (pts) with advanced
unresectable or metastatic HER2+ breast cancer, including pts with brain
metastases (BM), who have received 2 prior anti-HER2–based regimens.
In the pivotal HER2CLIMB trial, TUC added to T and C resulted in sta-
tistically signicant improvements in PFS and OS in HER2+ metastatic
breast cancer pts with and without BM (Murthy, NEJM 2020). We present
exploratory analyses of PFS by type of BM in HER2CLIMB.
HER2CLIMB (NCT02614794) pts were randomized 2:1 to receive
TUC or placebo combined with T and C. All pts had baseline brain MRI.
BM were classied as untreated, treated stable, or treated and progressing.
PFS per investigator and OS were analyzed by treatment arm in stable BM
pts (treated stable) and active BM pts (untreated + treated progressing),
using standard RECIST 1.1 assessing disease in both body and brain.
At baseline, 291 pts (48%) had BM: 198 (48%) in the TUC arm and 93
(46%) in the control arm. In pts with stable BM (n=117), median (95%
CI) PFS was 7.5 mo (5.4, 9.6) in the TUC arm vs 5.0 mo (2.0, 5.6) in the
placebo arm (HR: 0.56; 95% CI: 0.33, 0.96; P=0.03). In pts with active BM
(n=174), median PFS was 7.6 mo (5.7, 8.5) in the TUC arm vs 4.1 mo (3.1,
4.3) in the placebo arm (HR: 0.38; 95% CI: 025, 0.58; P<0.00001). In pts
with treated progressing BM (n=108), median PFS was 7.6 mo (5.7, 9.6) in
the TUC arm vs 4.1 mo (3.1, 4.3) in the placebo arm (HR: 0.36; 95% CI:
0.21, 0.63; P=0.0002). In pts with untreated BM (n=66), median PFS was
6.9 mo (5.5, 9.6) in the TUC arm vs 3.6 mo (1.5, 7.5) in the placebo arm
(HR: 0.47; 95% CI: 0.24, 0.92; P=0.02).
Addition of TUC to T and C signicantly improved PFS regardless of
BM type, indicating delay of progression not only in the body but also in
the brain. Patients with active BM (typically excluded from HER2+ MBC
trials) had substantially longer PFS with TUC treatment.
Reference:
1 Murthy et al. N Engl J Med. 2020;382:597–609.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
340
Toxicity of chemo- versus endocrine therapy in combination
with dual HER2-targeted therapy with trastuzumab and
pertuzumab plus ribociclib in patients with HER2 positive
and hormone-receptor positive metastatic breast
cancer - results from an Interim Safety Analysis of DETECT V
Fabienne Schochter1; Jens Huober1,2; Tanja Fehm3; Volkmar Müller4;
Brigitte Rack1; Marianne Just5; Jacqueline Sagasser6; Marcus Schmidt7;
Thomas Decker8; Andreas Hartkopf9; Andreas Schneeweiss10;
Thomas W. P. Friedl1; Wolfgang Janni1
1Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Ulm, Ulm,
Deutschland
2Brustzentrum, Kantonsspital St.Gallen, St. Gallen, Schweiz
3Klinik für Frauenheilkunde und Geburtshilfe, Heinrich-Heine-Universität
Düsseldorf, Düsseldorf, Deutschland
4Klinik und Poliklinik für Gynäkologie, Universitätsklinikum Hamburg-
Eppendorf, Martinistraße 52, Hamburg, Deutschland
5Onkologische Schwerpunktpraxis Bielefeld, Bielefeld, Deutschland
6Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Augsburg,
Augsburg, Deutschland
7Klinik für Frauenheilkunde und Geburtshilfe, Universitätsmedizin der Johannes
Gutenberg-Universität Mainz, Mainz, Deutschland
8Gemeinschaftspraxis für Hämatologie und Onkologie, Ravensburg,
Deutschland
9Department für Frauengesundheit, Universitätsklinikum Tübingen, Tübingen,
Deutschland
10Nationalen Centrum für Tumorerkrankungen (NCT), Universitätsklinikum
Heidelberg, Heidelberg, Deutschland
Background: Metastatic breast cancer (MBC) is a non-curable disease
and preserving quality of life is important for the patients. An emerging
body of evidence supports treatment options without chemotherapy in
HER2 positive and hormone-receptor positive metastatic breast cancer.
Methods: DETECT V / CHEVENDO is a prospective randomized phase
IIIa clinical trial to assess safety and ecacy of a dual human epidermal
growth factor receptor 2 protein (HER2)-targeted therapy with trastu-
zumab and pertuzumab combined with either chemotherapy (arm A) or
endocrine therapy (arm B) in patients with HER2- and hormone receptor
(HR)-positive MBC. With amendment no 1, the CDK4/6 inhibitor ribo-
ciclib was added as study treatment in both arms. is report analyses
the tolerability and safety of the study treatment for the rst 15 patients
randomized to both arms aer the addition of ribociclib.
Result: Overall, 232 adverse events (AEs) were reported, with 154 (66.4%)
AEs for patients in the chemotherapy arm and 79 (33.6%) AEs for patients
in the endocrine therapy arm. ere were 33 grade 3 AEs (21 in the che-
motherapy arm and 12 in the endocrine therapy arm) and 3 grade 4 AEs
(ileus, increased alanine aminotransferase, neutropenia) in the chemo-
therapy arm. Of the 9 serious adverse events (SAEs) observed, one was
death due to disease progression and 8 cases were classied as SAEs
because they required hospitalization. Only one of the observed SAEs was
regarded as a serious adverse reaction (SAR) – one patient in the endo-
crine arm developed chills suspected to be caused by trastuzumab.
Discussion: e observed AEs were within the expected range, with
diarrhea and neutropenia being the most frequent. Overall, this interim
analysis showed less toxicity in the endocrine therapy arm than in the
chemotherapy arm.
Conclusion: e combination of a dual HER2-targeted therapy with
endocrine treatment and ribociclib shows good tolerability and may be
a preferred treatment option for patients with HER2- and HR-positive
MBC, if further analyses of ecacy and quality of life support a favorable
risk-benet-ratio.
Disclosure Statement: e authors declare the following: Speaker fees/ honoraria:
Roche, Pzer, Novartis, Lilly, AstraZenica Consultat; none Research grants:
AstraZenica
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts26
353
Glutaminase inhibition as a therapeutic option for tamoxifen-
resistant breast cancer
Gerd Bauerschmitz; Friederike Steifensand; Julia Gallwas;
Carsten Gründker
Universitätsmedizin Göttingen UMG, Frauenklinik, Göttingen, Deutschland
Purpose: In the therapy of estrogen receptor α (ERα)-positive breast
cancer (BC), the focus is on hormone sensitivity targeting therapy with
selective estrogen receptor modulators (SERMs) such as 4-hydroxytamox-
ifen (4-OHT). However, this therapy is oen limited by development of
resistance. e upregulated glutaminolysis in BC cells could be used as
an additional therapeutic target. In this study, we have analyzed the use
of glutaminase inhibitor CB-839 to target the increased glutaminolysis.
Methods: Sublines of ERα-positive MCF7 and T47D BC cells were estab-
lished, which were developed to be resistant to 4-OHT. Cell viability was
analyzed using Alamar Blue. Induction of apoptosis was assessed by mea-
suring the mitochondrial membrane potential. Expression of c-Myc was
quantied by Western blot. Transient c-Myc gene silencing was conducted
using RNA interference.
Results: Co-treatment using 4-OHT and CB-839 showed signicantly
stronger inhibitory eects on viability compared to treatment with 4-OHT
or CB-839 only. Tamoxifen-resistant BC cells, compared to non-resistant
cells exhibited a reduced cell viability under CB-839 treatment. Further,
tamoxifen-resistant BC cells showed increased expression of proto-onco-
gene c-Myc which could be reduced by CB-839 treatment. Suppression of
c-Myc expression using specic siRNA completely abolished resistance to
4OH-tamoxifen.
Discussion: Our data suggest that combined treatments aecting metab-
olism of BC are suitable depending on cellularity and resistance status.
In addition, the anti-metabolic treatments aected expression of c-Myc,
a key player in the regulation of cancer cell metabolism and resistane
against 4-OHT.
Conclusion: Anti-metabolic treatment reduces c-Myc expression leading
to loss of tamoxifen-resistance. is fact should receive clinical attention
in the future.
Disclosure Statement: e authors declare no conict of interest.
354
Intrinsic Breast Cancer Subtypes depending on Participation
in Mammography Screening Program
Britta Mathys1; Iris Urbschat2; Joachim Kieschke2; Gerold Hecht1
1Referenzzentrum Mammographie Nord, Oldenburg, Deutschland
2Epidemiologisches Krebsregister Niedersachsen (EKN), Registerstelle,
Oldenburg, Deutschland
Background: Breast cancer in screening participants has shown favor-
able tumor characteristics and prognostic parameters compared to symp-
tom-detected breast cancer, even including interval cancers. Our aim
was to examine the distribution of the molecular breast cancer subtypes
considering the proliferation marker Ki-67 in participants and non-
participants of the German Mammography Screening Program (MSP) in
a population-based setting.
Methods: Data from the Epidemiological Cancer Registry of Lower
Saxony with diagnosis in year 2014 were analyzed. 953 cases of invasive
breast cancer among MSP participants and non-participants (aged 50-69
years, residing in two MSP-regions of Lower Saxony with 285.634 bien-
nially entitled women) were included. e group of the MSP participants
contained cancers that were detected by screening or in the interval of 24
month aer a negative screening. e group of non-participants included
all other cancers. A modied molecular subtyping of all tumors was per-
formed according to the S3-guidelines (categories for Ki-67: ≤ 10% = low,
11-24% = intermediate, ≥ 25% = high).
Result: Breast cancers of MSP participants were more oen HER2 neg-
ative (p = 0,03) and showed lower Ki-67 percentage scores (p = 0,0003)
compared to non-participants. According to this results and aer
exclusion of missing data (17%) the distribution of the intrinsic subtypes
was as follows: Luminal A (MSP participants 38,4% vs. non-participants
26,7%), Luminal A or B (26,7% vs. 22,1%), Luminal B (21,1% vs. 30,6%),
HER2 enriched (5,1% vs. 7,8%), triple-negative (8,8% vs. 12,8%). In both
groups the distribution of Ki-67 was associated with the analyzed prog-
nostic parameters with strongest association between Ki-67 and grading
(p < 0,0001).
Discussion: According to the S3-Guidelines an adjuvant chemother-
apy can be avoided due to a more favorable prognosis in the majority
of Luminal A type breast cancers. Assuming that both groups received
a guideline-based therapy, MSP participants could be treated with less
aggressive systemic therapy compared with cancers in non-participants.
Disclosure Statement: e authors declare the following: Dr. Hecht ist Leiter
des Referenzzentrums Mammographie Nord und Leiter der Screeningeinheit
Niedersachsen Nordwest, Dr. Mathys ist als Honorarkra im Referenzzentrum
Mammographie Nord tätig und arbeitet als Befunderin. Frau Urbschat und Herr
Kieschke haben keine wirtschalichen oder persönlichen Verbindungen im unten
genannten Sinne.
361
Association of polygenic risk scores with extreme ages at
onset of primary breast cancer in BRCA1/2 mutation carriers
Corinna Ernst1; Julika Borde1; Yael Laitman2; Barbara Wappenschmidt1;
Christoph Engel3; Rita Katharina Schmutzler1; Eitan Friedman2;
Eric Hahnen1
1Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology
(CIO), University Hospital Cologne, Cologne, Deutschland
2Oncogenetics Unit, Sheba Medical Center, Tel Aviv, Israel
3Institute for Medical Informatics, Statistics and Epidemiology, University of
Leipzig, Leipzig, Deutschland
Purpose: Clinical management of BRCA1/2 mutation carriers demands
for accurate age-dependent estimates of breast cancer (BC) risks.
erefore, the utility of polygenic risk scores (PRSs) for the discrimination
of extreme phenotypes with respect to age at onset, i.e., early diagnosis
(ED) before the age of 35 years and BC-free survival until the age of 60
years (late/no diagnosis, LD) in BRCA1/2 mutation carriers was assessed.
Methods: e overall BC PRS, estrogen receptor (ER)-positive BC PRS,
and ER-negative BC PRS as developed by Kuchenbaecker et al. [1] for BC
risk discrimination in female BRCA1/2 mutation carriers were employed
for PRS computation in a curated sample of 295 women of European
descent carrying pathogenic (class 4/5) variants in the BRCA1 (n=183)
or the BRCA2 gene (n=112), and were either diagnosed with primary BC
before the age of 35 years (ED, n=162, mean age at diagnosis: 28.3 years,
range: 20 to 34 years) or not aected by BC until the age of 60 years (LD,
n=133). Binomial logistic regression was applied to assess the association
of standardized PRSs with either ED or LD. Analyses were adjusted by BC
family history and localisation of pathogenic gBRCA1/2 variants in the
corresponding breast or ovarian cancer cluster regions.
Results: For BRCA1 mutation carriers, the standardized overall BC PRS
displayed the strongest association with ED (odds ratio (OR) = 1.62; 95%
condence interval (CI): 1.16–2.31, p = 0.007). For BRCA2 mutation car-
riers, the standardized PRS for ER-negative BC displayed the strongest
association with ED (OR = 2.27, 95% CI: 1.45–3.78, p < 0.001).
Discussion: Our results demonstrate the contribution of PRSs to the
development of extreme phenotypes of BRCA1/2 mutation carriers with
respect to age at primary BC diagnosis.
Conclusions: PRSs are essential prequisites for personalized BC risk pre-
diction in clinical management of healthy women with BRCA1/2 germline
mutations.
Reference:
[1] Kuchenbaecker, K. et al. Evaluation of polygenic risk scores for breast and
ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers. J Natl
Cancer Inst, 2017.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 27
426
The BEGYN study: Assessment of quantity and quality of
physical activity, tness, body composition, immunological
biomarkers, and psychological parameters during the rst
year after diagnosis of breast cancer
Cosima Zemlin1; Caroline Stuhlert1; Julia Theresa Schleicher1;
Carolin Wörmann1; Laura Altmayer1; Marina Lang1;
Laura-Sophie Scherer1; Ida Thul1; Carolin Müller1; Elisabeth Kaiser2;
Regine Stutz2; Sybelle Goedicke-Fritz2; Laura Ketter3; Gudrun Wagenpfeil4;
Michael Zemlin2; Georges Stegen3; Erich-Franz Solomayer1
1Saarland University Medical Center, Department for Gynecology, Obstetrics
and Reproductive Medicine, Homburg, Deutschland
2Saarland University Medical Center, Department for General Pediatrics and
Neonatology, Homburg, Deutschland
3University of Luxembourg, Department of Behavioural and Cognitive Sciences,
Institute for Health and Behaviour, Esch-sur-Alzette, Luxemburg
4Saarland University Campus Homburg, Institute for Medical Biometry,
Epidemiology and Medical Informatics (IMBEI), Homburg, Deutschland
Purpose: e BEGYN study prospectively examines the relationship
between physical activity and course of disease and therapy (e.g. dose
adjustments), laboratory parameters, tness, body composition and men-
tal health.
Methods: Non-metastatic breast cancer patients were recruited at the
breast center of the Saarland University Hospital. Before starting ther-
apy and aer 3, 6, 9 and 12 months, all patients are assessed by tread-
mill spiroergometry, routine laboratory, ow cytometry of leukocyte
subpopulations, cytokine proles in plasma (MagPix), body composition
(bioimpedance) and psychometry using standardized questionnaires on
quality of life, stress, mental health, depression, etc. (EORTC-QLQ (BR23,
C30), HADS, Distress ermometer, MDBF, SPG). Each patient wears a
tness tracker (Fitbit Charge 3™). Metabolic equivalents (METs) are calcu-
lated based on a daily exercise diary. Membership fees in sports clubs are
reimbursed. Registration number: DRKS00024829.
Results: Between 10/2019 and 01/2021 197 of 387 newly aected patients
met the inclusion criteria and 110 patients agreed to participate in the
BEGYN study. Age 54.1 +/- 11.8 years (mean, SD). 66 patients received
chemotherapy and 41 endocrine therapy exclusively. In 22 of 42 (52%)
patients that completed the one year follow up until Aug 2021, tness
(resting heart rate) was better at the end of the study than at the begin-
ning, in 16 (38%) it was worse. In contrast, the muscle mass decreased in
64 % of the patients and increased in 29%.
Discussion: e recruitment goal (n = 110) of the BEGYN study was
achieved. Initial results indicate that tness can increase even under onco-
logical therapy, whereas muscle mass decreased in the majority, even with
better tness during the year aer the diagnosis of breast cancer.
Conclusion: e BEGYN study will improve the understanding of the
relationship between physical activity and somatic and psychological vari-
ables in breast cancer and provide data to develop individualized training
recommendations for our patients.
Disclosure Statement: e authors declare no conict of interest.
429
A new approach (Hilotherapy®) to prevent chemotherapy –
induced Polyneuropathy (CIPN) - UPDATE
Trudi Schaper1; Maren Darsow1; Mahdi Rezai2; Petra Hegener3;
Günther Schmutz3
1Luisenkrankenhaus GmbH & Co KG, Düsseldorf, Deutschland
2European Breast Center Dr. Rezai, Düsseldorf, Deutschland
3MVZ Düsseldorf, Düsseldorf, Deutschland
Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is
an adverse eect of many commonly used chemotherapeutic agents, espe-
cially taxane-based regimen (Paclitaxel, nab-Paclitaxel, Docetaxel). CIPN
reduces patients health-related quality of life for years and oen results in
dose delay, dose reduction or treatment discontinuation. e preventive
use of controlled thermotherapy (Hilotherapy®) prevents CIPN.
Method:189 breast cancer patients used a new thermotherapy, a device
equiped with hand /foot cus to allow a constant cooling.
Continous cooling of extremities was performed 30 minutes before to
60minutes aer completing drug infusion with a temperature of 10-12°C.
CIPN symptoms were evaluated aer each cytotoxic cycle using common
terminology criteria for adverse events (CTCAE).
Sustainability of results was assessed by long-term datas (every 3 months).
151 patients used the prophylactic Hilotherapy® for each cytotoxic treat-
ment (Group 1: primary Prophylactic Hilotherapy® - pPHT).
38 patients used reactive secondary Hilotherapy® (Group 2: rSHT). Hands
and feet were cooled aer onset of symptoms of CIPN (grade 1-3).
Results:
Group pPHT: Out of 151 patients who used pPHT, 141 patients (93%)
developed none or mild symptoms of CIPN (grade 0-1). 9 patients (6 %)
reported grade 2, 1 patient grade 3 (0,8%) toxicity. 4 weeks aer last che-
motherapy, no patient suered grade 3 CIPN; grade 2 toxicities have been
reduced to 7 patients (6% to 4,7%). 69% described no symptoms (grade
0), 26,4% mild symptoms of CIPN (grade 1). 4 – 10 months aer chemo-
therapy 98% of patients have no CIPN>grade 1.
Group rSHT: Without using pPHT 90% of the patients developed CIPN
symptoms. 50% suered grade 3 2 CIPN. Using rSHT for all remaining
chemotherapies, progression of CIPN was stopped, reduction of toxici-
ties was seen. At last chemotherapy treatment grade 2 & 3 toxicities were
reduced from 50% to 25%.
Conclusions: Preventive Hilotherap prevents CIPN > grade 1 in 93% of
patients. No dose reductions or treatment discontinuation was necessary,
and quality of life is maintained.
Disclosure Statement: e authors declare no conict of interest.
436
Abemaciclib combined with adjuvant endocrine therapy
in patients with high risk early breast cancerwho received
neoadjuvant chemotherapy (NAC)
Tjoung-Won Park-Simon1; Miguel Martin2; Roberto Hegg3; Sung-Bae Kim4;
Michael Schenker5; Daniela Grecea6; Jose Angel Garcia-Saenz7;
Konstantinos Papazisis8; Quchang Ouyang9; Aleksandra Lacko10;
Berna Oksuzoglu11; James Reeves12; Meena Okera13; Laura Testa14;
Chikako Shimizu15; Ran Wei16; Tammy Forrester16; Maria Munoz16;
Annamaria Zimmermann16; Desiree Headley16; Stephen Johnston17
1Medizinische Hochschule Hannover, Hannover, Deutschland
2Hospital General Universitario Gregorio Marañon, Madrid, Spanien
3Clin. Pesq.e Centro, São Paulo, Brasilien
4Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republik
Korea
5Centrul de Oncologie Sf. Nectarie SRL, Craiova, Rumänien
6Institutul OncologicProf.Dr. Ion ChiricutaCluj-Napoca, Cluj-Napoca,
Rumänien
7Hospital Clinico San Carlos, Madrid, Spanien
8Euromedica - General Clinic of Thessaloniki, Thessaloniki, Griechenland
9Hunan Cancer Hospital, Changsha, China, VR
10Dolnoslaskie Centrum Onkologii, Wroclawski Uniwersytet Medyczny,
Breslau,Polen
11Dr.Abdurrahman Yurtaslan Ankara Oncology Training & Res Hosp,
Ankara,Türkei
12Florida Cancer Specialists/Sarah Cannon Research Institute SCRI,
FortMyers,USA
13Adelaide Cancer Centre, Kurralta Park, Australien
14Instituto DOr de Pesquisa e Ensino (IDOR), São Paulo, Brasilien
15Präfektur Tokio, National Center for Global Health and Medicine, Tokio, Japan
16Indianapolis, Eli Lilly and Company, Indianapolis, USA
17Royal Marsden NHS Foundation Trust, London, Vereinigtes Königreich
Background: monarchE (phase 3, open-label, randomized study evalu-
ating abemaciclib combined with adjuvant endocrine therapy [ET] com-
pared to ET alone in patients [pt] with HR+, HER2-, high risk early breast
cancer [EBC]) resulted in a statistically signicant improvement in inva-
sive disease-free survival (IDFS; HR=.713; 95%CI=.583, .871).
Methods: Pt with ≥4 positive nodes (LNS)/1-3 LNS and either Grade
3 disease, tumor size ≥5 cm or central Ki-67 ≥20% were eligible. Prior
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts28
chemotherapy (NAC, adjuvant, none) was a stratication factor. We
present results of the prespecied subgroup of pt who received NAC.
Results and Discussion: Of 5637 randomized pt, 2056 received NAC.
Chosen regimen included anthracycline +cyclophosphamide +taxane
for 84.8% and anthracycline+taxane for 4.4%. In pts who received NAC,
29.1% had tumors ≥5 cm at diagnosis, 36.7% had tumors with histologic
grade 3 and 55.2% had LNS ≥4+. Central Ki-67 prior to NAC was ≥20%
in 64.8% pt with available Ki-67 results (664 (32.3%) pt had missing Ki-67
results). A multivariate cox regression analysis of IDFS in intent-to-treat
(ITT) population identied prior chemotherapy as prognostic, suggesting
pt who received NAC were at risk of a worse outcome. For pt who received
NAC, abemaciclib+ET demonstrated treatment benet in terms of IDFS
vs ET alone (IDFS events: abemaciclib+ET=92; ET alone=148; HR=.614,
95%CI=.473, .797) with 2-year IDFS rates of 87.2% (95%CI=84.1, 89.8) vs
80.6% (77.0, 83.6). ere was also a benet in distant relapse-free survival
(DRFS) (DRFS events: abemaciclib+ET=77; ET alone=125; HR=.609,
95%CI=.459, .809), with 2-year DRFS rates of 89.5% (95%CI=86.7, 91.8)
vs 82.8% (79.3, 85.8).
Conclusions: Patients with HR+, HER2- EBC who received NAC were
at a higher risk of recurrence. In this subgroup, abemaciclib+ET demon-
strated a clinically meaningful treatment benet in IDFS and DRFS,
which was numerically greater than in the ITT population. Safety data
were consistent with abemaciclib safety prole.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
441
Comparison of clinical, histopathological, therapeutic
factorsand survival between 2510 male and 307634 female
patients with invasive breast cancer – results from a large
population-based cohort study in Germany
Marion Graf1; Michael Gerken1,2; Monika Klinkhammer-Schalke1,2;
Simone Schrodi3; Jutta Engel3; Armin Pauer1,2; Olaf Ortmann4;
Elisabeth C. Inwald4
1Tumour Center, Institute for Quality Management and Health Services
Research, University of Regensburg, Regensburg, Deutschland
2Bavarian Cancer Registry - Regional Centre Regensburg, Bavarian Health and
Food Safety Authority (LGL), Regensburg, Deutschland
3Munich Cancer Registry (MCR) at the Institute of Medical Information
Processing, Biometry, and Epidemiology, Ludwig-Maximilians-University,
Bavarian Cancer Registry - Regional Centre Munich, Bavarian Health and Food
Safety Authority, München, Deutschland
4University Medical Center Regensburg, Department of Gynecology and
Obstetrics, Regensburg, Deutschland
Purpose: To date few data on breast cancer in men are available. erapy
recommendations are mainly based on those for postmenopausal women.
Evidence suggests higher mortality in male breast cancer. e present
study compared clinical, histopathological and therapeutic factors as well
as survival rates between men and women with malignant neoplasms of
the breast.
Methods: In the present cohort study data from 18 German clinical
cancer registries were analyzed retrospectively. 2,510 male and 307,634
female patients with malignant neoplasms of the breast were included.
Results: Men showed signicantly worse prognostic factors at date of diag-
nosis, e.g. higher stage and positive lymphatic invasion. With a median
follow-up time of 8.8 years, 5-year overall survival rate in women was
80.4% vs. 69.6% in men. Hazard ratio derived from univariable Cox
regression was 1.759 (95 % CI: 1.652 - 1.873; p <0.001). In multivariable
Cox regression with adjustment for age at diagnosis, tumor side, histology,
stage, grading, lymphatic and venous invasion, hormone receptor status,
HER2/neu, Ki-67, and year of diagnosis the mortality risk for men was
still 1.322 times higher than for women (95 % CI: 1.241 - 1.407; p <0.001).
Also recurrence-free survival was worse in men. Comparing systemic
therapies in corresponding indication groups, treatment rates were 9.5%
to 23.8% lower in men than in women. e inclusion of systemic thera-
pies in the multivariable analysis did not change the dierence of mortal-
ity risk between men and women. However, when guideline-concordant
therapy was performed in men a similar treatment benet as in women
was observed.
Discussion: Even taking account dierences in patient and tumor charac-
teristics and treatment rates mortality risk remains higher in men. Other
inuences such as lifestyle or biological factors could play a role.
Conclusions: To explain the disparity between male and female breast
cancer survival and to nd possible improvements for male patients,
future projects should include lifestyle and biological factors.
Disclosure Statement: e authors declare no conict of interest.
479
Intraoperative circular resection of the breast in patients
withprimary breast cancer in stage 0 to III - experience
of a singular breast center
Wladimir Pauker
Rotenburg (Wümme), AGAPLESION DIAKONIEKLINIKUM ROTENBURG
gemeinnützige GmbH, Frauenklinik, Rotenburg (Wümme), Deutschland
Background: e circular resection of the adjacent breast tissue aer
tumor resection signicantly reduces the number of tumor-involved mar-
gins and thus both the number of repeated breast-conserving operations
and the number of mastectomies in patients with primary breast cancer
in stage 0-III.
Methods: From December 17, 2019 to July 9, 2021, 273 patients with pri-
mary breast cancer in stages 0 to III underwent breast-conserving sur-
gery. 176 (64.5%) (group I) patients were operated on with a degree of
complexity I to II according to Wallwiener D. et al.1, Breast-conserving
surgery (BEO). In the other 97 (35.5%) (Group II) patients, oncoplastic
techniques with degrees of complexity III to V were used. All patients
received either specimen radiographs or sonographies intraoperatively to
reduce the likelihood of postoperative resections. 43 (44.3%) of 97 breast
cancer patients received a circular resection of the breast tissue adjacent
to the tumor in addition to advanced oncoplastic techniques and indepen-
dent of intraoperative controls of marginal distances.
Result: e number of patients in group I who required repeated
breast-conserving surgery or mastectomy was 39 / 22.1% of 176. In group
II patients with complex oncoplastic techniques with and without intra-
operative resections, the number of repeated resections was equal to
Operations 8 / 14.8% of 54 and 4 / 9.3% of 43, respectively.
Conclusion: We were able to determine that the use of complex onco-
plastic breast-conserving operations leads to a reduction in the number of
repeated interventions from 22.1% to 14.8% and the additional intraoper-
ative resection reduces the number of repeat operations by more than half
from 22.1% to 9.3%.
Reference:
1. Wallwiener, D.; Hahn, M.; Marx, M.; P. Renner, S.; Y. Brucker, S.; Homann,
J:Plastische Chirurgie. Die Bedeutung der Onkoplastik in der modernen
Senologie. Geburtshilfe und Frauenheilkunde2015; 75(10): 977–990
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 29
504
Safety interim analysis (SIA) of the phase III postneoadjuvant
SASCIA study evaluating sacituzumab govitecan (SG) in
patients (pts) with primary HER2-negative breast cancer (BC)
at high relapse risk after neoadjuvant chemotherapy (NACT)
Frederik Marmé1; Claus Hanusch2; Jenny Furlanetto3; Patrick Morris4;
Theresa Link5; Carsten Denkert6; Peter Andreas Fasching7;
Christian Jackisch8; Silvia Antolín9; Christine Solbach10; Philippe Aftimos11;
Jens Huober12; Michael Untch13; Marija Balic14; Mattea Reinisch15;
Jens-Uwe Blohmer16; Anthony Concalves17; Julia Rey3; Thomas Büchele3;
Sibylle Loibl3
1Medical Faculty Mannheim, Heidelberg University, University Hospital
Mannheim, Mannheim, Deutschland
2Rotkreuzklinikum München, München, Deutschland
3German Breast Group, Neu-Isenburg, Deutschland
4Beaumont Hospital, Dublin, Irland
5Department of Gynecology and Obstetrics, Technische Universität Dresden,
Dresden, Deutschland
6Institute of Pathology, Philipps University Marburg and Marburg University
Hospital (UKGM), Marburg, Deutschland
7Universitätsklinikum Erlangen, Erlangen, Deutschland
8Sana Klinikum Oenbach GmbH, Oenbach am Main, Deutschland
9Complejo Hospitalario Universitario A Coruña-Hospital Teresa Herrera (CHUAC),
Servicio de Oncología Médica (planta baja), Coruña, Spanien
10Universitätsklinikum Frankfurt, Frankfurt am Main, Deutschland
11Clinical Trials Conduct Unit, Institut Jules Bordet - Université Libre de Bruxelles,
Brüssel, Belgien
12Kantonsspital St.Gallen, Brustzentrum, Departement Interdisziplinäre
medizinische Dienste, St. Gallen, Schweiz
13Helios Klinikum Berlin-Buch, Berlin, Deutschland
14Medical University of Graz, Clinical Department of Oncology, Graz, Österreich
15Kliniken Essen-Mitte, Essen, Deutschland
16Gynäkologie mit Brustzentrum, Charité-Univesitätsmedizin Berlin
17Institute Paoli-Calmettes, Marseille, Frankreich
Background: SASCIA (NCT04595565) is an ongoing phase III study ran-
domising pts with HER2- BC and residual disease aer NACT or hor-
mone receptor (HR)+ with a CPS+EG score ≥3 or 2 and ypN+ aer NACT
to SG or treatment of physician´s choice (TPC, capecitabine, platinum,
observation). We present the results of the pre-planned SIA.
Methods: e analysis was performed aer the rst 50 randomized pts
had completed 4 therapy cycles. Pts were included if they received ≥2
cycles, were observed ≥6 wks or discontinued earlier. Adverse events
(AEs) grade (G) 1-4, G3-4 and compliance (reductions, delays, discontin-
uation) between arms were assessed.
Result: At the time of the analysis, 142 pts were randomized, 88 were
included in the SIA. 45 pts received SG, 32 capecitabine, 11 were observed.
Median age was 46 (24-71) in SG vs 51 (32-74) yrs in TPC arm, median
BMI 25.8 (20.0-42.6) vs 23.8 (18.2-35.4) kg/m2, more pts in SG arm had
a Ki67>20% (N=29, 64.4% vs N=21, 48.8%); 30 (66.7%) vs 29 (67.4%)
were HR-, 15 (33.3%) vs 14 (32.6%) HR+. 44 (97.8%) vs 29 (72.5%) had
hematological AEs G1-4, 25 (55.6%) vs 0 G3-4; 45 (100%) vs 36 (83.7%)
had non-hematological AEs G1-4, 15 (33.3%) vs 9 (20.9%) G3-4. No death
occurred. 6 (13.6%) pts under SG vs 3 (9.4%) under capecitabine discon-
tinued therapy prematurely; 30 (66.7%) vs 13 (43.2%) had ≥1 dose delay,
due to hematological (N=21, 46.7% vs N=3, 10.0%) and non-hematologi-
cal AEs (N=3, 6.7% vs N=7, 23.3%); 12 (26.7%) vs 9 (28.1%) had ≥1 dose
reduction (hematological N=6, 13.3% vs N=1, 3.1%; non-hematological
N=5, 11.1% vs N=6, 18.8%).
Discussion: SG showed a higher rate of AEs compared to TPC, which
includes observation only. AEs, especially G3-4 AEs rate were in line with
the known safety prole of SG and led to more dose delays.
Conclusion: AEs due to SG therapy were well manageable using the rec-
ommended supportive measures. e study continues as planned.
Disclosure Statement: e authors declare that there are conicts of interest.
e connections were submitted to the congress organizer KUKM GmbH and
KUKM can disclose them if needed.
506
Remote-monitoring among patients undergoing
chemotherapy in the out-patient setting for early detection of
infections
Heike Jansen1; Anna Eichhorn1; Jannina Schaller1; Veronika Langhans1;
Kirsten Große Lackmann2; Marko Wilhelm3; Marion Kiechle1
1Klinikum rechts der Isar, TU München, Frauenklinik und Poliklinik, München,
Deutschland
2Spital Zollikerberg, Zollikerberg, Schweiz
3AIM - Apps in Medicine GmbH, München, Deutschland
Background: Due to immunosuppressive oncologic therapy patients are
at risk for infections. In case of COVID-19, patients have a high risk even
to die due to this infection, especially when they have a progressive dis-
ease. But also dose-reductions, -modications or postponing of chemo-
therapy cycles result in disease-progression and are associated with early
deaths (1,2). In this study we oer patients at risk user-friendly technolo-
gies for transmitting biosignal-data and patient reported outcome moni-
toring (PROM) data for early detection of infections.
Methods: We designed a monocenter prospective cohort study using
PROM via app and remote monitoring via photoplethysmography (PPG).
e application of these technologies enables an early detection of infec-
tions and therefore initiation of medical interventions. e study is con-
ducted as feasibility analysis; primary endpoints are adherence (according
to wearing time) and technical robustness.
Result: We expect study results in 4th quarter 2022.
Discussion: e applied user friendly technologies can be used in the
out-patient setting for transmission of biodata and symptoms; but also
for a better communication between patients and physicians. is results
in medical interventions at an early stage for treatment of infections. is
study is conducted in a cooperation with the department of cardiology,
using the infrastructure of the TUM telemedicine-center. Long-term
objective ist to establish an expandable remote-monitoring infrastructure
for the public health sector.
Conclusion: By the use of remote-monitoring and PROM, we obtain an
increase in safety for cancer patients undergoing immunosuppressive
oncologic therapy during COVID-19 pandemia.
Indication of source:
1 Warner JL, CCC19, ASCO 2020
2 Hatsy S, Inzidenz und Prädiktoren von Chemotherapie-Modikationen und
deren Einuss auf das Überleben von Patientinnen mit Ovarialkarzinom;
Dissertation TUM 2020
Disclosure Statement: M. Kiechle und K. Große Lackmann sind Anteilseigner
der AIM - Apps in Medicine GmbH. Eine Forschungsförderung erfolgt durch das
Bayerische Staatsministerium für Wissenscha und Kunst, sowie anteilig durch
das Bundesministerium für Bildung und Forschung im Rahmen der Förderung
des nationalen Pandemie Kohorten Netzwerks (NAPKON) im Netzwerk Universi-
tätsmedizin (NUM).
548
Eects of an Oncological Exercise Therapeutical Structure on
the Fatigue Syndrome of Female Breast Cancer Patients in a
Comprehensive Cancer Center
Franziska Hollnberger1; Anna Lorenz2; Monika Siegrist1;
Freerk T. Baumann2
1Fakultät für Sport- und Gesundheitswissenschaften Technische Universität
München, Lehrstuhl für Präventive und Rehabilitative Sportmedizin, München,
Deutschland
2Universität zu Köln, Klinik I für Innere Medizin Centrum für Integrierte
Onkologie Aachen Bonn Köln Düsseldorf Uniklinik Köln, Köln, Deutschland
Background: ere is growing evidence that physical activity has a pos-
itive eect in reducing side eects such as fatigue and improving Quality
of Life (QoL) in Breast Cancer patients. Recently, exercise therapy was
implemented in the S3 Guidelines for Breast Cancer patients. More stud-
ies are necessary which focus on a clinical set up, to provide evidence for
changes in treatment structures and increase the awareness in Health
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts30
insurance companies to secure nancial support. e aim of the study is
to evaluate the OTT (Oncological training and exercise therapy) program
at the University Hospital in Cologne to provide patients with access to
evidence-based exercise therapy.
Methods: Breast cancer patients which participated in the OTT program
between 2012 and 2020, were dived in two groups. e intervention group
(n = 46) trained on average between one and two days per week whereas
the control group (n = 58) trained less than once a week with a combi-
nation of strength and endurance exercise. All patients lled out various
questionnaires on physical activity, fatigue, and QoL at the anamnesis (T0)
and the end of the program (Tx).
Result: Signicant eects where only found for physical fatigue, reduced
activity and QoL among time but not between groups. However, a positive
trend towards reduced levels of fatigue and better QoL was visible in the
intervention group. A relation between the development of fatigue and
change of QoL was detected.
Discussion: e evaluation of an existing care structure brings limita-
tions such as dierent time between measurements or arbitrary allocation
to groups, which can lead to non-signicant results between groups. In
accordance with several meta-analyses, trends of this study indicate a pos-
itive eect of physical activity to reduce fatigue and improve QoL.
Conclusion: In the future, it is suggested to conduct more implementa-
tion studies in the clinical setup based on individual training. e OTT
program should be expanded to alleviate the side eects of cancer diag-
nosis and/or therapy.
Disclosure Statement: e authors declare no conict of interest.
553
Association between treatment duration and overall survival
in early-stage HER2+ breast cancer patients receiving
extended adjuvant therapy with neratinib in the ExteNET trial
Friedrich Overkamp1,2; Beverly Moy3; Bruno Coudert4; Alvin Wong5;
ArleneChan6
1onkowissen.de GmbH, Digital Health, Würzburg, Deutschland
2OncoConsult Overkamp, Berlin, Deutschland
3Massachusetts General Hospital Cancer Center, Boston, USA
4Centre Georges François Leclerc, Dijon, Frankreich
5Puma Biotechnology Inc., Los Angeles, USA
6Breast Cancer Research Centre-WA & Curtin University, Perth, Australien
Background: Completion of planned treatment has been shown to
improve clinical outcomes. In the ExteNET trial (NCT00878709), where
diarrhea prophylaxis was not mandated, 17% of patients (pts) discontin-
ued neratinib early due to diarrhea. is compares with 3.3% of pts from
the CONTROL trial (NCT02400476) who used a neratinib dose-escala-
tion strategy. Prior analyses have shown improved invasive disease-free
survival (iDFS) in pts who completed planned duration of neratinib ther-
apy in ExteNET. Here we assess outcomes, including overall survival (OS),
for pts who completed planned therapy in 3 groups from ExteNET: intent-
to-treat (ITT) population; pts with hormone receptor-positive (HR+) dis-
ease who initiated neratinib within 1y aer prior trastuzumab (HR+/≤1y,
the population neratinib is approved for in the EU); and HR+/≤1y with
residual disease post-neoadjuvant therapy (no pathologic complete
response [pCR]).
Methods: Pts with early-stage HER2+ breast cancer received oral nera-
tinib 240mg/d or placebo aer trastuzumab-based (neo)adjuvant ther-
apy. Pts who completed neratinib therapy (dened as ≥11m or cessation
of neratinib if recurrence occurred prior to 11m) were compared with
placebo (all randomized pts). iDFS and OS were analyzed using Kaplan-
Meier methods; hazard ratios (HR) with 95% condence intervals (CI)
were estimated using Cox proportional-hazards models. Data cuto: July
2019.
Result: ere were 2840 pts in the ITT population, 1334 pts in the
EU-label population (HR+/≤1y) and 295 pts with HR+/≤1y and no
pCR. In patients who completed 1 year neratinib, the 8-year OS rate was
improved by 2.0% (ITT, HR 0.78, 95%-CI 0.58-1.04), 5.8% (HR+/≤1y; HR
0.49, 95%-CI 0.29-0.78) and 13.2% (HR+/≤1y, no pCR; HR 0.29, 95%-CI
0.01-0.68), respectively, compared to placebo.
Discussion: Completion of planned neratinib was associated with
improvements in iDFS and OS in all groups evaluated.
Conclusion: ese descriptive ndings suggest that pts who receive
the recommended duration of treatment of 1y with neratinib may have
improved outcomes.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
572
Berlin Young Patients – Implementing a registry for breast
cancer in women before the age of 40
Anna Maria Hage; Mara Daniel; Friedrich Kühn; Therese Pross;
DorotheeSpeiser; Maria Margarete Karsten
CharitéUniversitätsmedizin Berlin, Klinik für Gynäkologie mit Brustzentrum,
Berlin, Deutschland
Background: e risk of developing breast cancer before the age of 40
is low. However, younger age at diagnosis is oen associated with worse
prognosis. Until now, no certain phenotype correlating with younger
age could be established. Furthermore, issues such as genetic predispo-
sitions, fertility and pregnancy, therapy-associated early menopause, and
extended survivorship period require special attention in young breast
cancer patients. As current management strategies are not age-based, we
aim for a better understanding of the particularities of breast cancer in
young women.
Methods: 556 patients with breast cancer or ductal carcinoma in
situ (DCIS) diagnosed before the age of 40 and treated at Charité –
Universitätsmedizin Berlin were identied retrospectively (2008 - 2019).
Data from clinical patient records on information such as tumor stage at
diagnosis, pathologic features, genetics, therapy, recurrence, and survival
will be analyzed. A process to obtain consent to examine tumor tissues
from past surgeries is being prepared, as well as a process to include
patients prospectively.
Result: First results will be available in January 2022.
Discussion: is registry may help to identify characteristics, particular-
ities and needs of young women with breast cancer or DCIS. With this
knowledge, more specied approaches for clinical care can be explored
and potential new recommendations for age-based management strate-
gies can be considered.
Conclusion: e implementation of this registry will provide important
data about the small percentage of patients who develop breast cancer
before the age of 40. is registry will contribute to a better understanding
of the specic clinical characteristics and needs of this group of patients.
Disclosure Statement: e authors declare no conict of interest.
590
Analysis of single-cells using reverse phase protein array
(RPPA) technology
Mahdi Rivandi1; Liwen Yang1; André Franken1; Tanja Fehm1;
DieterNiederacher1; Berthold Gierke2; Michael Pawlak2; Hans Neubauer1
1Department of Obstetrics and Gynecology, Heinrich Heine University of
Duesseldorf, Duesseldorf, Deutschland
2NMI TT Pharmaservices, Protein Proling, Reutlingen, Deutschland
Background: erapy with Capivasertib, a potent pan-AKT inhibi-
tor, does not lead to response in all breast cancer patients with PIK3CA
mutated tumor cells. One reason may be that the eect of the mutation
does not translate into modulation of protein activity, making protein
analysis in single tumor cells highly interesting. is project aims to evalu-
ate protein expression and activation of dierent therapy target proteins in
the PI3K/AKT/mTOR signaling pathway at single-cell level using reverse
phase protein array (RPPA) technology.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 31
Methods: MCF-7 cells were treated with Capivasertib (5µM) to increase
phosphorylation of AKT1 protein. Single cells stained with NucBlue
(Hoechst) were micromanipulated with the CellCelectorTM device and
lysed in dierent cell lysis buers. Lysates were aspirated into a glass cap-
illary and printed in triplicates onto a Zeptosens chip. ese were blocked
and incubated with primary (p-AKT and AKT-pan) and uorescence
labelled secondary antibodies, respectively. Signals were detected by a
Zeptoreader and the treatment-to-untreated control ratios (TCR) were
calculated for pAkt and Akt total protein. Data were analyzed by Image
J soware. Western blot was conducted to conrm expression levels and
phosphorylation of Akt1.
Result: Spotting of triplicates is highly reproducible with a signal dier-
ence below 10%. e optimal amount and ratio of lysis buer is 20nL of 1:1
CLB: CSLB buer with the spotting volume of 2nL. e humidity during
spotting and the other picking/printing parameters were optimized. As
expected, TCR of pAkt/Akt is more than twofold elevated (243%) in single
treated MCF-7 cells compared to the control group in three independent
experiments. e ratios determined with single cells are in line with west-
ern blot data.
Conclusion: We have established a new and highly sensitive method to
measure expression and phosphorylation of treatment relevant proteins in
single cells to measure activation of key cancer driving signaling pathways.
Disclosure Statement: e authors declare no conict of interest
607
The Impact of Irradiation and Lipotransfer on Healthy
Mammary Cells after Breast-Conserving Surgery
Chiara-Sophia Kutz1; Tina Jost2; Luitpold Distel3;
Annika Kengelbach-Weigand1; Theresa Hauck4; Raymund E. Horch4
1Universitätsklinikum Erlangen, Plastisch- und Handchirurgische Klinik,
Forschungslabor, Erlangen, Deutschland
2Universitätsklinikum Erlangen, Strahlenklinik, Erlangen, Deutschland
3Universitätsklinikum Erlangen, Strahlenklinik, Strahlenbiologie, Erlangen,
Deutschland
4Universitätsklinikum Erlangen, Plastisch- und Handchirurgische Klinik,
Erlangen, Deutschland
Background: A promising option for reconstructing tissue defects aer
breast-conserving surgery (BCS) for breast cancer treatment is the stem-
cell-assisted lipotransfer (CAL) because of the postulated regenerative
potential of included adipose-derived stem cells (ADSCs). However,
knowledge about dierent eects of ADSCs in combination with radio-
therapy on healthy mammary cells and their microenvironment remains
incomplete.
Methods: To simulate a CAL aer BCS, an indirect coculture model
with the healthy mammary epithelial cell line MCF-10A and the human
broblast cell line MRC-5 was established. e cells were cocultured, irra-
diated with 2 and 5 Gy and treated with conditioned medium (CM) of
the ADSC cell line ASC-52telo. ereaer, the eects on transmigration
capability and on survival (ow cytometry) of MCF-10A were analyzed.
Additionally, mRNA levels of cytokines (e.g. IL1B), mesenchymal markers
(e.g. FN1) and extracellular matrix markers (e.g. MMP2) were tested.
Result: In all groups, ADSC-CM stimulated transmigration of MCF-10A.
is eect was less pronounced aer irradiation with 5 Gy. In contrast to
transmigration, ADSC-CM had no eect on survival rates.
Combined treatment with ADSC-CM and irradiation with 2 and 5 Gy
induced a higher expression of FN1 in MCF-10A. Cocultivation of MCF-
10A with MRC-5 stimulated IL1B-expression in MRC-5.
Discussion: ADSC-CM enhances transmigration of MCF-10A which
leads to the assumption of an increased cell-activity and hence a better
integration of the transplant into the mammary tissue.
Increased expression-levels of FN1 due to treatment with ADSC-CM and
irradiation can imply the induction of epithelial-mesenchymal transition
(EMT)-associated transcription changes which have to be validated by
additional testing of other EMT-markers.
Conclusion: e study shows single and combined eects of ADSCs and
radiotherapy on healthy mammary cells in their microenvironment which
should be considered in the application of CAL.
Disclosure Statement: e authors declare no conict of interest.
608
Trastuzumab deruxtecan (T-DXd) combinations in patients
with HER2-positive advanced or metastatic breast cancer: a
phase 1b/2, open-label, multicenter, dose-nding and
dose-expansion study (DESTINY-Breast07)
Hans-Christian Kolberg1; Fabrice André2; Erika Hamilton3; Sherene Loi4;
Peter Schmid5; Carey Anders6; Tinghui Yu7; Sarice Boston7; Celina D’cruz7;
Pia Herbolsheimer7; Komal Jhaveri8
1Breast and Gynecologic Cancer Center, Marienhospital, Department of
Gynecology and Obstetrics, Bottrop, Deutschland
2Goustave Roussy, Université Paris-Sud, Villejuif, Frankreich
3Sarah Cannon Research Institute/ Tennessee Oncology, Nashville, TN, USA
4Peter MacCallum Cancer Center, Melbourne, VIC, Australien
5Barts Cancer Institute, Centre for Experimental Cancer Medicine, London,
Vereinigtes Königreich
6Duke Cancer Institute, Durham, NC, USA
7AstraZeneca Pharmaceuticals, Gaithersburg, USA
8Memorial Sloan Kettering Cancer Center, New York, NY, USA
Background: HER2-targeted therapies have improved survival in patients
(pts) with HER2+ advanced/metastatic breast cancer (mBC) but chal-
lenges remain, including resistance to current HER2-targeted therapies.
In the DESTINY-Breast01 trial, T-DXd demonstrated ecacy, with an
objective response rate (ORR) of 61.4% and median progression-free sur-
vival (mPFS) of 19.4 mo in pts with previously treated HER2+ advanced/
mBC [1]. Data from an earlier cuto of this trial supported approval of
T-DXd in the US, Europe, and Japan. In a subgroup analysis of 24 pts
with stable BM, T-DXd showed preliminary ecacy, with mPFS of 18.1
mo [2]. Here, we describe a trial evaluating the safety and preliminary
antitumor activity of T-DXd monotherapy and combinations in pts with
HER2+ advanced/mBC, including pts with stable and active brain metas-
tases (BM).
Methods: DESTINY-Breast07 (NCT04538742) is a global, multicenter,
open-label, phase 1b/2 trial to evaluate the safety, tolerability, and antitu-
mor activity of T-DXd monotherapy and combinations in pts with HER2+
advanced/mBC. It consists of a T-DXd monotherapy module (0) and 5
combination modules of T-DXd plus (1) durvalumab, (2) pertuzumab, (3)
paclitaxel, (4) durvalumab + paclitaxel, or (5) tucatinib, in pts with no
or stable BM. Modules 6 (T-DXd + tucatinib) and 7 (T-DXd monother-
apy) include pts with active BM. Modules 1 - 5 each consist of 2 parts:
dose nding (part 1) and dose expansion (part 2). Modules 0, 6, and
7 include part 2 only. e primary endpoints are determination of the
recommended phase 2 doses (part 1 only) and safety and tolerability of
T-DXd and combinations (parts 1 and 2). Secondary endpoints include
ORR, PFS, PFS2, duration of response, and overall survival (part 2 only)
and pharmacokinetics and immunogenicity (parts 1 and 2).
Result: n/a
Discussion: n/a
Conclusion: n/a
Indication of source:
1. Modi, S., et al. 2021. 81(4 Supplement): p. PD3-06-PD3-06.
2. Jerusalem, G., et al. Annals of Oncology, 2020. 31: p. S63-S64.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts32
611
Feasibility of automated breast ultrasound (ABUS) for
intraoperative margin control on surgical specimens in breast
conserving surgery
Maria Eleni Hatzipanagiotou1; Deborah Huber1; Valeria Gerthofer1;
Katharina Ried1; Blanca Roca Ripoll1; Olaf Ortmann1; Stephan Seitz1
1University Medical Centre Regensburg, Department of Gynecology and
Obstetrics, Regensburg, Deutschland
Background: As breast-conserving surgery (BCS) has become stan-
dard for treatment of breast cancer, there is need for new technologies
to improve intraoperative margin assessment. Close or positive margins
during BCS lead to additional surgeries, treatment delay, additional stress
for patients, and healthcare cost. In this study we evaluated the feasibility
of ABUS to conduct specimen ultrasound in BCS.
Methods: In this monocentric, non-interventional study, specimens of 40
women who received BCS were examined via ABUS. e specimens were
xed by the surgeon on a KliniTray and put into the corresponding plas-
tic box. A construction with isotonic saline solution, gel pads and ABUS
membranes was invented to produce images of breast cancer specimens
using ABUS while avoiding contact between the transducer and the iso-
tonic water bath. Evaluation of the ABUS images was carried out by two
independent physicians trained on ABUS evaluation.
Result: In 37 (92,5%) cases the generated ABUS images were considered
of good quality by the authors. Measured tumor size with ABUS was big-
ger than with Hand-Held Ultrasound (HHUS) (mean 22,9 vs. 18,1 mm,
KI 2,38-7,35, p<0,05). e measured tumor size by ABUS was comparable
to the nal pathological tumor size (KI -0,84-4,53, p=0,17), meanwhile
there was a signicant dierence between the measured tumor size via
HHUS and pathological tumor size (KI -5,35- -1,03, p=0,005).
Discussion: e development of a method to use ABUS in specimen
ultrasound provides the opportunity to conduct further studies regarding
the accuracy of ABUS in specimen ultrasound and to evaluate whether
the generated images will be of advantage in perioperative sonography.
Conclusion: ABUS seems to be a suitable method to conduct specimen
ultrasound.
Disclosure Statement: e authors declare no conict of interest.
656
Awareness, oer, and use of psychosocial services by breast
cancer survivors in Germany – Results of the prospective
multi-centre study BRENDA II. Part 1
Susanne Singer1; Wolfgang Janni2; Felix Flock3; Ricardo Felberbaum4;
Thorsten Kühn5; Lukas Schwentner2; Elena Leinert2; Davut Dayan2;
AchimWöckel6; Tanja Schlaiß6
1University Medical Centre Mainz, Mainz, Deutschland
2Ulm, Deutschland
3Memmingen, Deutschland
4Kempten, Deutschland
5Esslingen, Deutschland
6Würzburg, Deutschland
Purpose: is study examined the pattern of psychosocial care in breast
cancer survivors.
Methods: In a prospective study with measurements before surgery, one
month, 8 months and 5 years thereaer, we examined the proportion
of breast cancer survivors who were aware about, had been oered and
received various types of psychosocial services from psychologists, social
workers, doctors, self-help groups etc. e degree of helpfulness per ser-
vice among users was ascertained. Determinants of awareness, oer and
use were investigated using binary logistic regression analyses.
Results: Among 456 breast cancer survivors who participated until 5
years, psychological services (in the hospital, rehabilitation clinic, cancer
counselling centre, private psychotherapy practice) were known by 91%,
oered to 68%, and used by 55% of patients. Social services (in the hospi-
tal, rehabilitation clinic, cancer counselling centre) were known by 86%,
oered to 65%, and used by 51%. Women ≥65 years were less likely to
be informed about (odds ratio (OR) 0.2) and get oers for psychosocial
services (OR 0.4 for social and 0.5 for psychological services) than women
<65 years. e services rated most helpful were social services in the hos-
pital, psychological counselling by a consultant and psychotherapy in pri-
vate practices.
Conclusion: ese ndings underline the importance of psychosocial
support by physicians in addition to the “professional” mental health and
social care providers. ey also show that elderly women in need for sup-
port might be in danger of not being well-informed about the services
available.
Disclosure Statement: e authors declare no conict of interest.
658
Eect of social services on nancial and role functioning
and employment in breast cancer patients with high social
burden – Results of the prospective multi-centre study
BRENDA II. Part 2
Davut Dayan1,1; Susanne Singer2; Elena Leinert1; Wolfgang Janni1;
Thorsten Kühn3; Felix Flock4; Ricardo Felberbaum5; Lukas Schwentner1;
Achim Wöckel6
1Ulm, Deutschland
2Mainz, Deutschland
3Esslingen, Deutschland
4Memmingen, Deutschland
5Kempten, Deutschland
6Würzburg, Deutschland
Background: is study examined the eects of social services (social
work care) on nancial and role functioning (work and leisure time) in
breast cancer (BC) patients 5 years aer diagnosis.
Methods: In a prospective study with analysis before surgery (t1), before
the start of adjuvant treatment (t2), aer completion of adjuvant treat-
ment (t3) and 5 years aer surgery (t4), we examined the proportion of
BC survivors with nancial or role problems and those who are employed.
We also examined how frequently social services were known about, as
well as oered and used.
Results: Of 456 BC survivors, 33% had nancial and 22% had role func-
tional problems at t4.
Of those with nancial problems, 70% were oered social services and
61% used it. Of those without nancial problems, 63% were oered coun-
seling and 60% used it. Patients with nancial problems were not more
likely to be informed about social services (odds ratio (OR) 1.1, P=0.84)
and were not more likely to use it (OR 1.3, P=0.25).
Patients with role function problems were oered social services in 73%
and used it in 61%, whereas 59% of patients without suprathreshold prob-
lems were oered it and 44% used it. Survivors with role function prob-
lems were more likely to be oered social services (OR 1.7, P=0.02) and to
use it (OR 1.6, P=0.03).
Of the 456 participants, 255 were younger than 65 years. Of these, 70%
were employed at t4. Patients with employment before surgery and who
had received social services were more likely to be employed 5 years aer
diagnosis than those without counseling (OR 1.9, p=0.04).
Conclusion: ese ndings underscore the importance of social services
among BC patients with nancial and social problems. Recipients of social
services are more likely to be employed than non-recipients.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 33
721
Quality of life and therapy-adherence among breast cancer
patients: a randomized, prospective, multicenter clinical trial
on the eect of a digital software application
Heike Jansen1; Lalesu Kumas1; Wiebke Heldmaier1;
Kirsten Große Lackmann2; Anna Eichhorn1; Marko Wilhelm3;
Marion Kiechle1
1Klinikum rechts der Isar, TU München, Frauenklinik und Poliklinik, München,
Deutschland
2Spital Zollikerberg, Zollikerberg, Schweiz
3AIM - Apps in Medicine GmbH, München, Deutschland
Background: For women with breast cancer, disease and therapy come
along with loss of quality of life. Furthermore the burden of the therapy
and its side eects oen result in unauthorized discontinuation of the
therapy by patients. Non-adherence rates to endocrine therapy (ET) range
from 31% to 73% (1). Consequently these patients have a poorer progno-
sis due to recurrence, progression and cancer deaths.
Methods: We designed a randomized, prospective, multicenter clinical
trial on the eect of the use of the companion-app „Meine Busenfreundin
on quality of life and therapy-adherence among breast cancer patients,
compared to standard of care. With validated questionnaires, patient
reported outcome monitoring data on quality of life, distress and ther-
apy-adherence are collected. In case of pathologic values, the attend-
ing breast center gets advised to intervene according to individual
requirements.
Result: Enrollment starts in 3rd quarter 2022. We expect study results in
2nd quarter 2025.
Discussion: Psychoeducation to increase therapy-adherence turned out
not to be eective. Positive eects were shown in subgroup analyses for
bidirectional communication. Moreover the use of apps with reminder
functions can increase adherence to cancer therapy. Our intention within
this project is to improve care of patients with primary breast cancer.
Conclusion: Responsible use of medical applications is a resonable com-
plement for integrative treatment: this study is conducted to show, that
side eects can be reduced and therapy-adherence increased.
Indication of source:
1 Murphy et al, Adherence to adjuvant hormonal therapy among breast cancer
survivors in clinical practice: a systematic review. Breast Cancer Res Treat.
2012 Jul;134(2):459–78.
Disclosure Statement: M. Kiechle und K. Große Lackmann sind Anteilseigner der
AIM - Apps in Medicine GmbH. Eine Forschungsförderung wurde beim Innova-
tionsfonds der Gemeinsamen Bundesausschusses beantragt.
745
Multiparametric Characterization of Circulating Tumor Cells
from Metastatic Breast Cancer Patients for Selection of
Targeted Therapies
André Franken1; Bianca Behrens2; Florian Reinhardt1; Liwen Yang1; Mahdi
Rivandi1; Ellen Honisch1; Francesco Marass3; Niko Beerenwinkel3; Irene
Esposito4; Frederic Dietzel5; Nikolas H. Stoecklein2; Dieter Niederacher1;
Tanja Fehm1; Hans Neubauer1
1Department of Obstetrics and Gynecology, University Hospital and Medical
Faculty of the Heinrich-Heine University Duesseldorf, Düsseldorf, Deutschland
2General, Visceral and Pediatric Surgery, University Hospital and Medical Faculty
of the Heinrich Heine University Duesseldorf, Düsseldorf, Deutschland
3Department of Biosystems Science and Engineering, ETH Zurich, Basel, Schweiz
4Institute of Pathology, University Hospital and Medical Faculty of the Heinrich-
Heine University Duesseldorf, Düsseldorf, Deutschland
5Department of Diagnostic and Interventional Radiology, University Hospital
and Medical Faculty of the Heinrich-Heine University Duesseldorf, Düsseldorf,
Deutschland
Background: Over the last decades targeted therapy has become the pre-
ferred approach to treat breast cancer. However, the predictive utility of
the primary tumor is limited and obtaining serial biopsies of metastatic
lesions is challenging. us, the analysis of liquid biopsies e.g. circulating
tumor cells (CTCs) is an appealing diagnostic concept.
Methods: First, CTCs of ve metastatic breast cancer patients were
enriched with the CellSearch and analyzed by whole exome sequencing
(WES). Next, one of the patients was selected and monitored by longi-
tudinal and multiparametric liquid biopsy analyses over more than three
years, including WES, array comparative genome hybridization, RNA
proling and in vitro drug testing of CTCs.
Result: In CTCs from all patients, mutations addressable by targeted ther-
apies were detected, including mutations that were not detected in biop-
sies of the primary tumor. By further analysis of the CTCs from the index
patient, the clonal evolution of the tumor was retraced and resistance
mechanisms were analyzed. e AKT1 E17K mutation was uncovered as
the driver of the metastatic process and a chemotherapy resistant subclone
was identied. Drug testing on the patients CTCs conrmed the ecacy
of drugs targeting the AKT1 pathway. Based on this CTC characteriza-
tion, a targeted therapy including everolimus was selected. During this
therapy, CTC numbers dropped by 97.3% and the disease remained stable
determined by computer tomography/magnetic resonance imaging.
Conclusion: We propose that such a longitudinal and multiparametric
analysis of liquid biopsies has the potential to identify individual targets
for eective therapies, to monitor treatment response, and to optimize
the clinical outcome eventually. Furthermore, from a scientic point of
view, such studies can promote the understanding of the biology of CTCs
during dierent treatment regimens and thereby further help to optimize
treatment of all patients.
Disclosure Statement: e authors declare no conict of interest.
748
PGRMC1 binds to prohibitins upon progestin treatment and
promotes ERα activation in breast cancer cells
Nadia Stamm1; Yingxue Bai1; Marina Ludescher1; Dieter Niederacher1;
Tanja Fehm2; Hans Neubauer1
1Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Düsseldorf,
Forschungslabor, Düsseldorf, Deutschland
2Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Düsseldorf,
Düsseldorf, Deutschland
Background: Women receiving combined menopausal hormone therapy
(HT) are at a higher risk for developing breast cancer (BC). e progestins
used in HT have been previously demonstrated to stimulate progesterone
receptor membrane component 1 (PGRMC1), a multifunctional protein
associated with worse survival of BC patients. Here, we describe a poten-
tial mechanism by which PGRMC1 contributes to BC progression via
estrogen receptor alpha (ERα) activation.
Methods: We investigated PGRMC1 interaction partners with special
focus on PGRMC1 phosphorylation using BC cells expressing phosphor-
ylation decient PGRMC1 variants and CRISPR/Cas9 based PGRMC1-
knockout BC cells. Since we identied PGRMC1 interaction partners
which play a role in ERα-signaling, we investigated the activation the ERα
target gene TFF1 by qPCR aer treatment of BC cells with progestins.
Further, we measured proliferation of BC cells at conditions of PGRMC1
overexpression and progestin stimulation and aer pre-treatment of cells
with the ERα-inhibitor fulvestrant.
Results: e ERα-repressors PHB1 and PHB2 were identied as inter-
action partners of PGRMC1 upon treatment with certain progestins in
BC cell lines. Further, increased interaction between PGRMC1 and PHBs
correlated with decreased binding of PHBs to ERα, indicating a contribu-
tion of PGRMC1 to the ERα-signaling network. Consequently, stimula-
tion of PGRMC1-overexpressing cell lines lead to increased proliferation
and TFF1 transcription, whereas pre-inhibition of ERα with fulvestrant
completely abolished the proliferative eect conducted by PGRMC1.
Discussion: We provide strong evidence for an involvement of PGRMC1
in activation of ERα-signaling upon treatment with certain progestins
via inhibition of the ERα-repressors PHB1 and PHB2. Subsequent ERα-
mediated oncogenic signaling increases cell proliferation and may con-
tribute to BC progression.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts34
Conclusion: Our study emphasizes the implication of PGRMC1 in the
ERα regulation network and suggests PGRMC1 as a potential therapeutic
target.
Disclosure Statement: e authors declare no conict of interest.
751
Tumour inltrating lymphocytes as prognostic factor in breast
cancer
Kathleen Schüler1; Daniel Bethmann2; Tilmann Lantzsch3;
Christoph Uleer4; Volker Hanf5; Susanne Peschel6; Jutta John7;
Marleen Poehler8; Jörg Buchmann9; Karl-Friedrich Bürrig10;
Edith Weigert11; Eva Johanna Kantelhardt1; Christoph Thomssen1;
Martina Vetter1
1Martin-Luther-Universität Halle-Wittenberg, Universitätsklinikum Halle, Klinik
und Poliklinik für Gynäkologie, Halle (Saale), Deutschland
2Martin-Luther-Universität Halle-Wittenberg, Universitätsklinikum Halle, Institut
für Pathologie, Halle (Saale), Deutschland
3Krankenhaus St. Elisabeth und St. Barbara, Klinik für Gynäkologie, Halle (Saale),
Deutschland
4Praxis für Gynäkologische Onkologie Uleer, Hildesheim, Deutschland
5Klinikum Fürth, Klinik für Gynäkologie
6Bernward Krankenhaus, Klinik für Gynäkologie, Hildesheim, Deutschland
7Klinikum Hildesheim, Klinik für Gynäkologie, Hildesheim, Deutschland
8Klinikum Wolfenbüttel, Klinik für Gynäkologie
9Martha-Maria Krankenhaus, Institut für Pathologie, Halle (Saale), Deutschland
10Institut für Pathologie Hildesheim, Hildesheim, Deutschland
11Pathologie Amberg, Amberg, Deutschland
Background: Tumor inltrating lymphocytes (TILs) are considered to
have prognostic and predictive value for patients with early breast can-
cer. e aim of this study was to evaluate the distribution of TILs and the
association with survival.
Methods: From a prospective, multicenter cohort of 1,270 breast can-
cer patients (PiA, Prognostic Assessment in routine application, NCT
01592825), 1,136 samples were evaluated for TIL following the recom-
mendations of the international TILs working group. TILs were grouped
(low <10%, intermediate 10-60% and high >60%) and scored as a continu-
ous parameter per 10% increment. Primary objective was the distribution
of TILs. Second objective was the association of TILs with recurrence free
interval (RFI) and overall survival (OS). e median observation time was
62 months (1-123).
Result: More than 60% TILs were detected in 1.5% of hormone receptor
(HR) positive and HER2 negative tumors, 9.7% of HER2 positive tumors
with any HR status and 18.8% of triple negative breast cancer (TNBC).
In the HER2 positive group with more than 60% TILs, no RFI event was
detected, and with less than 60% TILs, 15% of the patients had an RFI
event. e probability of OS was 94% (TILs >60%) and 81% (TILS ≤60%).
For TNBC and the same TIL cut o, 88% had no RFI and OS event, com-
pared to 70% with no event for RFI and 74% for OS. Applying 10% incre-
ments of TILs, the multivariate analysis revealed a hazard ratio of 0.89
(95% CI 0.796-1.007) for RFI and a signicant hazard ratio of 0.89 (95%
CI 0.794-0.997) for OS. A 10% increment of TILs in HER2 positive tumors
led to an increase of RFI (0.79, 95% CI 0.601-1.043) and OS (0.71, 95% CI
0.533-0.955, p<0.05) and in TNBC an increase of RFI (0.90, 95% CI 0.773-
1.063) and OS (0.94, 95% CI 0.795-1.115). ere was no eect of TILs for
patients with HR positive tumors.
Discussion: In our cohort, TILs were ascertained as an independent even
not signicant prognostic factor for patients with HER2 positive and TN
tumours.
Conclusion: TILs are a prognostic factor in breast cancer. Suitable cut os
for clinical implementation need to be found.
Disclosure Statement: e authors declare no conict of interest.
756
Correlation between single gene expression and age at
diagnosis in primary breast cancer patients
Anne-Sophie Heimes1; Walburgis Brenner1; Annette Hasenburg1;
Jan G. Hengstler2; Marcus Schmidt1
1Universitätsmedizin Mainz, Klinik und Poliklinik für Geburtshilfe und
Frauengesundheit, Mainz, Deutschland
2Leibniz-Institut für Arbeitsforschung an der TU Dortmund, Toxikologie /
Systemtoxikologie, Dortmund, Deutschland
Background: Elderly women represent a signicant proportion of breast
cancer patients. In previous gene expression analyses we identied a sig-
nicant association between the patients age at surgery and certain meta-
genes, particularly immune-associated metagenes (B-cell metagene, T-cell
metagene) and the luminal metagene. In this study we analysed the cor-
relation between single genes, associated to the above mentioned meta-
genes, and patients age at surgery.
Methods: Using microarray-based gene expression analysis with the
Aymetrix HG-U133A array, we examined a possible correlation between
age at surgery and the expression of the single genes IGKC, CD 20 and CD
8, being associated to the B-cell and T-cell metagene respectively, in 461
breast cancer patients. Furthermore, a possible interrelation between the
ESR1 expression, as a representative single gene of the luminal metagene,
and age was investigated. Correlations were calculated using Spearman
correlation coecient.
Results: ere was a strong, signicant correlation between ESR1 expres-
sion and older age at surgery (r=0.548; p<0.001). Moreover, there was an
inverse, statistically signicant correlation between patients age at diag-
nosis and the above-mentioned immune-associated single genes such
as IGKC (r=-0.275; p<0.001), and CD 20 (r=-0.122; p<0.008) as part of
the B-cell metagene as well as CD 8 (r=-0.175; p<0.001), representing the
T-cell metagene.
Conclusion: Gene-expression analysis of 461 primary breast cancer
patients shows a close positive correlation between age at surgery and
ESR1 expression, whereas immune associated genes such as IGKC, CD20
and CD 8 correlate inversely with age. ese ndings should be consid-
ered when selecting the appropriate adjuvant treatment strategy.
Disclosure Statement: e authors declare no conict of interest.
769
Curcumin as a complementary approach to the Treatment of
metastatic breast Cancer
Andre Rotmann1,2
1Gynäkologisch/Onkologische Praxis, Zentrum für komplementäre Onkologie,
Rodgau, Deutschland
2Gynäkologisc/Onkologische Praxis, Zentrum für komplementäre Onkologie,
Rodgau, Deutschland
Complementery medicine is a big issue in oncological therapy in the
recent time Ecacy and safety of curcumin in combination with pacli-
taxel in patients with advanced, metastatic breast cancer: We assessed the
ecacy and safety of iv. curcumin infusion in combination with paclitaxel
in patients with metastatic and advanced breast cancer. A randomized,
double-blind, placebo-controlled, parallel-group comparative clinical
study was conducted. 150 women with advanced and metastatic breast
cancer were randomly assigned to receive either paclitaxel plus placebo
or paclitaxel plus curcumin intravenously for 12 weeks with 3 months of
follow-up. e primary outcome was determined based on the objective
response rate (ORR), as assessed by the Response Evaluation Criteria in
Solid Tumors (RECIST). e secondary outcomes were progression-free
survival (PFS), time to tumor progression (TTP), time to tumor treatment
failure (TTTF), safety, and quality of life.
Results: e intention-to-treat (ITT) analysis revealed that the ORR of
curcumin was signicantly higher than that of the placebo (51% vs. 33%,
p<0.01) at 4 weeks of follow-up. e dierence between the groups was
even greater when only patients who had completed the treatment (61%
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 35
vs. 38%, odds ratio ==2.64, p<0.01) were included. A superior eect of cur-
cumin vs placebo was observed in both patients who had completed the
treatment and all patients included in the ITT analysis, 3 months aer ter-
mination of the treatment. No other signicant dierences were observed
between the curcumin and the placebo groups, except for fatigue (3 vs. 10
patients, respectively; odds ratio ==3.7, p = 0.05). However, the patients
self-assessed overall physical performance was signicantly higher with
curcumin than the placebo during the treatment and at the end of the
follow-up, suggesting better tolerance in the curcumin group.
Conclusions: Overall, treatment with curcumin in combination with
paclitaxel was superior to the paclitaxel placebo combination with respect
to ORR and physical performance aer 12 weeks of treatment.
Disclosure Statement: e authors declare no conict of interest.
903
Evaluation of Local Recurrence and Overall Survival
inPatients with Triple-negative Breast Cancer depending
onSurgical Procedure
Sophie Räpple1; Michael Gerken2,3; Maria Hatzipanagiotou1;
PeterUgocsai1; Monika Klinkhammer-Schalke2,3; Armin Pauer2,3;
Olaf Ortmann1; Stephan Seitz1
1Department of Gynecology and Obstetrics, University Medical Center
Regensburg, Regensburg, Deutschland
2Tumour Centre, Institute for Quality Management and Health Services
Research, Regensburg, Deutschland
3Bavarian Cancer Registry, Bavarian Health and Food Safety Authority, Regional
Centre Regensburg, Regensburg, Deutschland
Background: e primary operative therapy for triple-negative breast
cancer (TNBC) includes breast-conserving therapy (BCT) and mastec-
tomy (MXT). While data for other immunohistochemical types of breast
cancer is oen available, there is a lack of studies concerning the tri-
ple-negative subtype, that prove the long-term results and thus the onco-
logical safety of the treatment, especially aer neoadjuvant chemotherapy
(NACT). is retrospective cohort study examined the inuence of surgi-
cal intervention with or without radiation treatment on local recurrence,
overall survival and recurrence-free survival.
Methods: e study included 724 patients diagnosed with TNBC between
2010 and 2018, of whom 591 received BCT and 133 MXT. Within the
group of MXT 61 women received radiation treatment and 72 did not.
Statistical analyses were performed using IBM SPSS Statistics (version
25). e test procedures used were Chi-square independence test, Kaplan-
Meier analysis including log-rank test and uni- and multivariable Cox-
regression analysis.
Result: ere was a highly signicant advantage of BCT + RT over both
types of surgery without radiation treatment for overall survival and
recurrence-free survival in both univariable (p = <0.001; p = <0.001) and
multivariable analyses (p = <0.001; p = <0.001). In contrast no statistically
signicant dierence between the types of surgery was found for the end
point of local recurrence. e subgroup analysis of NACT presented an
advantage of BCT + RT over MXT + RT in all three end points.
Discussion: Some studies show no signicant dierences in outcomes of
local therapy but use data of treatments from the last decade. More recent
work shows consistent results but oen lacks information on local recur-
rence as an important endpoint.
Conclusion: is work provides evidence that when receiving radiation
therapy both BCT and MXT oer at least equivalent oncological safety
in TNBC. Aer undergoing NACT and radiation BCT seems not only
equivalent but superior to MXT.
Disclosure Statement: e authors declare no conict of interest.
931
Tumor Necrosis Factor-α (TNFα) Stimulate Triple Negative
Breast Cancer Stem Cells to Promote Intratumoral Invasion
and Neovasculogenesis in the Liver
Harini Narasimhan1; Francesca Ferraro1; Ralf Weiskirchen2; Elmar
Stickeler1; Jochen Maurer1
1Aachen, University Hospital Aachen RWTH, Gynecology and Obstetrics, Aachen,
Germany, Deutschland
2Aachen, University Hospital Aachen RWTH, Institut für Molekulare
Pathobiochemie, Aachen, Germany, Deutschland
Background: Triple Negative Breast Cancer (TNBC) represents the most
aggressive breast cancer subtype. Although cancer stem cells (CSCs)
are a minor fraction of all cancer cells, they are highly cancerous when
compared to their non-stem counterparts, playing a major role in tumor
recurrence and metastasis. Angiogenic stimuli and the tumor environ-
ment response are vital factors in cancer metastasis. However, cause and
eect in tumor angio- genesis and the “see-and-soil”-paradigm in TNBC
are still poorly understood.
Methods: We used primary TNBC stem cells to investigate the eect of
TNFα on. Methods include sphere forming assays, qPCR, Western Blots,
proliferation-and invasion-assays, tube formation assays, orthotopic
xenogras and immunohistochemistry.
Result: In this study we demonstrate TNFα eects on primary triple nega-
tive breast cancer stem cells (BCSCs). TNFα stimulation increased mesen-
chymality of BCSCs in an intermediate EMT state, enhanced proliferation,
self-renewal, and invasive capacity. TNFα-treatment elicited BCSC sig-
naling on endothelial networks in vitro and increased network forming
capacity of the endothelial cells. Our ndings further demonstrate that
TNFα stimulation in BCSCs has the ability to instigate distinct cellular
communication within the tumor microenvironment inducing intratu-
moral stromal invasion. Further, TNFα-treatment in BCSCs induced a
pre-metastatic niche through breast-liver organ cross talk by inducing
VCAM-1 enriched neovasculogenesis in the liver of tumor-bearing mice.
Discussion: is is the rst time the eect of TNFα induced breast-liver
organ cross talk showing increased liver neo-vasculogenesis is described
as part of a “seed-and-soil”-paradigm.
Conclusion: Overall, TNFα is an important angiogenic target to be con-
sidered in breast cancer progression to attenuate any angiogenic response
in the tumor environment which could lead to secondary organ metastasis.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts36
936
Sacituzumab govitecan (SG) versus treatment of physicians
choice (TPC) in patients (pts) with previously treated
metastatic triple-negative breast cancer (mTNBC): Final
results from the phase 3 ASCENT study
Rudolf Weide1; Aditya Bardia2; Sara Tolaney3; Delphine Loirat4;
Kevin Punie5; Mafalda Oliveira6; Hope Rugo7; Adam Brufsky8;
Kevin Kalinsky9; Javier Cortes10; Joyce O’shaughnessy11;
Veronique Dieras12; Lisa Carey13; Luca Gianni14; Martine Piccart-Gebhart15;
Sibylle Loibl16; Yanni Zhu17; See-Chun Phan17; Sara Hurvitz18
1Praxis für Hämatologie und Onkologie, Koblenz, Deutschland
2Department of Hematology/Oncology, Massachusetts General Hospital Cancer
Center, Harvard Medical School, Boston, USA
3Medical Oncology, Dana-Farber Cancer Institute, Boston, USA
4Medical Oncology Department and D3i, Institut Curie, Paris, Frankreich
5Department of General Medical Oncology and Multidisciplinary Breast Centre,
Leuven Cancer Institute, Leuven, Belgien
6Medical Oncology Department and Breast Cancer Group, Vall dHebron
University Hospital and Vall dHebron Institute of Oncology (VHIO), Barcelona,
Spanien
7Department of Medicine, University of California San Francisco Helen Diller
Family Comprehensive Cancer Center, San Francisco, USA
8Magee-Womens Hospital and the Hillman Cancer Center, University of
Pittsburgh Medical Center, Pittsburgh, USA
9Winship Cancer Institute, Emory University, Atlanta, USA
10International Breast Cancer Center, Quiron Group, Barcelona, Spanien
11Baylor University Medical Center, Texas Oncology, Dallas, USA
12Department of Medical Oncology, Centre Eugène Marquis, Rennes, Frankreich
13Lineberger Comprehensive Cancer Center, University of North Carolina,
ChapelHill, USA
14Medical Oncology, Gianni Bonadonna Foundation, Milan, Italien
15Medical Oncology Department, Institut Jules Bordet and lUniversité Libre de
Bruxelles, Bruxelles, Belgien
16Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-
Krankenhaus, Frankfurt, Deutschland
17Department of Clinical Development, Gilead Sciences Inc, Foster City, USA
18Department of Medicine, Division of Hematology/Oncology, David Geen
School of Medicine, University of California, Los Angeles, USA
Background: Treatment goals for pts with metastatic breast cancer
include extended survival and improved quality of life (QoL). SG received
FDA approval for pts with mTNBC who received ≥2 prior chemotherapies
(at least 1 in the metastatic setting). In the pivotal phase 3 ASCENT study
(NCT02574455), SG demonstrated a signicant survival benet over sin-
gle-agent chemotherapy TPC in the primary analysis (Bardia NEJM 2021)
and QoL (Loibl ESMO 2021). With additional follow up, we present the
nal data on ecacy, including overall survival (OS), safety, and QoL.
Methods: Pts with mTNBC refractory or relapsing aer ≥2 prior chemo-
therapies with at least 1 in the metastatic setting were randomized 1:1 to
receive SG (10 mg/kg IV on days 1 and 8, every 21 days) or TPC (capecit-
abine, eribulin, vinorelbine, or gemcitabine) until disease progression or
unacceptable toxicity. Primary endpoint was progression-free survival
(PFS), key secondary endpoints included OS, safety, and health-related
QoL. Safety was analyzed in pts who received ≥1 dose of study drug.
Result: At nal database lock SG (n=235) vs TPC (n=233) signicantly
improved median PFS (5.6 vs 1.7 mo; P<0.0001) and median OS (12.1 vs
6.7 mo; P<0.0001). In the safety population (n=482), key treatment-re-
lated grade ≥3 adverse events with SG (n=258) vs TPC (n=224) were diar-
rhea (11% vs 0.4%), neutropenia (52% vs 33%), anemia (8% vs 5%), and
febrile neutropenia (6% vs 2%).
Discussion: SG showed clinically meaningful and statistically signicant
improvements vs TPC in OS and QoL.
Conclusion: e analysis based on the nal database lock of ASCENT
conrms the superior survival outcomes of SG over single-agent chemo-
therapy, with a manageable safety prole and improvement in QoL for
pts with mTNBC in the 2L+ setting. ese ndings reinforce SG as an
eective treatment option for this pt population.
Indication of source:
1 Bardia et al. NEJM 2021; 384:1529-1541
2 Loibl et al. ESMO 2021; abstract 257P
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
954
The SURVIVE-study – a randomized phase 3 liquid-biopsy
based breast cancer surveillance trial
Thomas W. P. Friedl1; Sophia Huesmann1; Tatjana Braun1; Angelina Fink1;
Tanja Fehm2; Volkmar Müller3; Klaus Pantel4; Brigitte Rack1;
WolfgangJanni1
1Frauenklinik, Universitätsklinikum Ulm, Ulm, Deutschland
2Universitätsklinikum Düsseldorf, Frauenklinik, Düsseldorf, Deutschland
3Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für
Gynäkologie, Hamburg, Deutschland
4Institut für Tumorbiologie, Universitätklinikum Hamburg-Eppendorf, Hamburg,
Background: Aer patients with early breast cancer have completed pri-
mary therapy, current guidelines limit routine surveillance in breast can-
cer survivors to clinical surveillance and breast imaging. Screening for
distant metastases is initiated only in patients with specic symptoms.
Methods/Clinical Trial Design: e SURVIVE study, funded by the
German Federal Ministry of Education and Research, is a controlled phase
3 superiority trial, in which 3500 patients with intermediate-to-high risk
early breast cancer will be randomized 1:1 to guideline-based standard fol-
low-up surveillance versus intensied, liquid-biopsy guided surveillance.
Patients in the liquid-biopsy guided surveillance arm will be repeatedly
tested for the standard tumor markers CA 27.29, CA 125 and CEA, as well
as for circulating tumor cells and circulating tumor DNA. Pre-specied
abnormal ndings of any of the liquid biopsy markers indicative of mini-
mal residual disease (MRD) will trigger staging examinations including a
CT scan of the chest and abdomen and a bone scan. If the tumor staging
shows disease recurrence, the patients will receive guideline-based diag-
nostic measures and treatment; otherwise, the patients will continue liq-
uid-biopsy marker testing.
e two primary objectives of the SURVIVE study are to determine
whether the intensied, liquid-biopsy guided breast cancer surveillance
leads to a better overall survival and to assess the lead-time eect com-
pared to the standard surveillance arm. Secondary objectives include the
evaluation of invasive disease-free survival, distant disease-free survival,
quality of life, as well as sensitivity and specicity for the detection of
MRD by the liquid biopsy markers.
Result: n/a
Discussion: n/a
Conclusion: e SURVIVE study is a long-awaited breast cancer surveil-
lance trial based on promising liquid biopsy markers, which – if successful
- will lead to a paradigm shi in the current follow-up care of medium and
high-risk early breast cancer survivors.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 37
984
Tackling endocrine resistance:In vitroinvestigations
of novel ERα antagonists with a dual-target mechanism
Patricia Grabher; Nikolas Hörmann; Ronald Gust
Universität Innsbruck, Pharmazie, Pharmazeutische Chemie, Innsbruck,
Österreich
Background: 1 in 11 women in Europe is diagnosed with breast cancer
in their lifetime. Although progress has been made in the treatment of
hormone-dependent breast cancer in recent decades, intrinsic or acquired
resistances are an increasing problem. erefore, we synthetically opti-
mize known selective estrogen receptor modulators/degrader in such
a way that they target not only the common ligand binding site of the
estrogen receptor alpha (ERα) but also the co-activator binding site at the
surface of receptor with the aim of circumventing resistance mechanisms.
Methods: In-vitro investigations were carried out in hormone- dependent
MCF-7 cells, resistant and sensitive to Tamoxifen, as well as in hor-
mone-independent and ER-negative MDA-MB-231 cells. Furthermore,
we used uorine as a tracer and developed a high-resolution continuum
source electrothermal molecular absorption spectrometry (MAS) method
to quantify the intracellular drug content.
Result: We yielded IC50 values in the low µM range (IC50= 0.07- 0.5 µM)
in the wildtype MCF-7 as well as the Tamoxifen resistant MCF-7 cell line
(IC50= 0.08- 1.57 µM) and we observed no activity in the MDA-MB-231
cell line.
Discussion: For the interpretation of the intracellular eects
(ER-interaction and resulting cytotoxicity) it is necessary to know the
cellular uptake kinetic and the drug accumulation in the tumor cells.
e MAS method was validated with 5-Fluorouracil as a reference and
the results of the new ERα antagonists were correlated with inhibition of
ER-dependent transcription and observed cytotoxicity.
Conclusion: We could therefore prove that our substances are able to cir-
cumvent Tamoxifen resistance. Furthermore, as we observed no activity
in the MDA-MB-231 cell line, it indicates that we have achieved ER selec-
tivity with these substances.
Disclosure Statement: e authors declare no conict of interest.
1004
Decision-making criteria for the choice of 1st line
CDK4/6-inhibitor therapy for HR+/Her2- breast cancer
in Germany: DECISIONext
Dominique Finas1; Claudia Quiering2
1Gemeinschaftskrankenhaus Havelhöhe, Klinik für Frauenheilkunde und
Geburtshilfe, Berlin, Deutschland
2Novartis Pharma GmbH, Nürnberg, Deutschland
Purpose: AGO Breast recommendations 2021 propose endocrine-based
therapy as the 1st therapy option for HR+, MBC, if there is no threat of
organ failure. Since 11/2016, CDK4/6i plus endocrine therapy is an
option for 1st L therapy. is data collection intend to show which therapy
decisions are made and why in dierent patient groups with 1st L MBC.
Subsequent therapy may require molecular tumor characterization. How
oen molecular testing is done with MBC is largely unknown.
Methods: Retrospective data collection was carried out at 40 gynaeco-/
oncological centers in Germany. Data of 391 pts with HR+/HER2- MBC
wereanonymously recorded, treated between 01.01. and 30.06.2021 and
whostherapy decision for a 1st L therapy was made. Questions to be
answered are:
To what extent do dierent patient characteristics, previous treatment
and course of tumor inuence the choice of 1st L therapy?
Factors that inuenced therapy decision?
Frequency of molecular testing in met. situation and target parameters?
Results/Discussion: Of 391 pts, 17.4% were pre- and 82.5% postmeno-
pausal. 40.4% of the pts had de novo disease, 59.6% had (neo)adjuvant
pretreatment, 56.7% had (neo)adjuvant chemo. 36.5% of the (neo)adju-
vant treated pts relapsed during ongoing adjuvant therapy, another 8.2%
within 1 y aer completion of adjuvant therapy. Of these endocrine resis-
tant pts, treatment with CDK4/6i was not more frequent with fulvestrant
than with AI. In 32.7% of the pts, a molecular test was carried out in the
met. situation, mostly in 9.5% for PIK3CAm and in 21% for BRCAm. As
1st L therapy in the met. situation, 86.2% received a CDK4/6i, 6.6% che-
motherapy and 6.4% endocrine monotherapy. Pts on endocrine mono-
therapy are older and more likely to have solitary bone mets. Pts receiving
1st L chemotherapy are more likely to have lung and liver mets., but these
are not more likely to be symptomatic. e most common reported rea-
sons for choosing the CDK4/6i are “long experience with the substance
(48.8%) and “data situation” (45.5%). Endocrine resistance played a role in
CDK4/6i selection in only 8% of pts.
Disclosure Statement: e authors declare no conict of interest.
1027
GeparPiPPa- A randomized, open-label, phase II trial
comparing neoadjuvant trastuzumab, pertuzumab and
endocrine therapy +/- the PI3K inhibitor inavolisib in patients
(pts) with HER2+/HR+, PIK3CA mutant early breast cancer (BC)
Sibylle Loibl1; Mattea Reinisch2; Carsten Denkert3; Andreas Schneeweiss4;
Sabine Seiler1; Peter Andreas Fasching5; Claus Hanusch6; Theresa Link7;
Vesna Bjelic-Radisic8; Jens Huober9; Michael Untch10; Christian Jackisch11;
Christine Solbach12; Jens-Uwe Blohmer13; Kerstin Rhiem14;
Thomas Büchele1; Valentina Nekljudova1; Sherene Loi15
1German Breast Group, Neu-Isenburg, Deutschland
2Evang. Kliniken Essen-Mitte, Essen, Deutschland
3Institut für Pathologie, Philipps Universität Marburg und Universitätsklinikum
Marburg (UKGM), Deutschland
4Nationales Centrum für Tumorerkrankungen, Universitätsklinikum und
Deutsches Krebsforschungszentrum, Heidelberg, Deutschland
5Universitätsklinikum Erlangen, Erlangen, Deutschland
6Rotkreuzklinikum München, München, Deutschland
7Department of Gynecology and Obstetrics, Technische Universität Dresden,
Dresden, Deutschland
8Helios Universitätsklinik Wuppertal, Universität Witten/Herdecke, Wuppertal,
Deutschland
9Kantonsspital St.Gallen, Brustzentrum, Departement Interdisziplinäre
medizinische Dienste, St. Gallen, Schweiz
10Helios Kliniken Berlin-Buch, Berlin, Deutschland
11Sana Klinikum Oenbach, Oenbach, Deutschland
12University Hospital Frankfurt, Frankfurt, Deutschland
13Gynäkologie mit Brustzentrum, Charité-Universitätsmedizin Berlin, Berlin,
Deutschland
14Zentrum Familiärer Brust- und Eierstockkrebs, Universitätsklinikum Köln, Köln,
Deutschland
15Peter MacCallum Cancer Centre, Victoria Center, Melbourne, Australien
Background: PIK3CA mutations indicate a lower response to chemo-
therapy and anti-HER2 therapy, especially in HER2+/HR+ tumors (Loibl
S 2014 and 2016). Crosstalk exists between key signaling pathways (ER,
HER2 and PI3K) and inhibition of PI3K results in the activation of HER2-
pathway (Serra V 2011). e phase III Solar-1 study demonstrated a sig-
nicant improvement in progression-free survival with the addition of
alpelisib to fulvestrant in PIK3CA mutant metastatic BC (André F 2019).
GeparPiPPa investigates the ecacy and safety of inavolisib, an oral pure
PI3Kα inhibitor, in patients with HER2+/HR+ and PIK3CA-mutated BC
in the neoadjuvant setting.
Trial design: GeparPiPPa (NCT 05306041) is a multicenter, open-label,
phase II study. 170 pts with cT1c – cT3 early BC, centrally conrmed
HER2+ and HR+-status as well as a PIK3CA tumor mutation (by NGS)
will be randomized 1:1 to receive 6 cycles of tamoxifen or an aromatase
inhibitor (1x1/d orally, day 1-21 q3w) +/- gonadotropin-releasing hor-
mone analogue plus pertuzumab/trastuzumab (subcutaneous formula-
tion [1200 (600) mg/600 mg on d1, q3w]) without or with inavolisib (9mg
1x1/d orally, day 1-21 q3w). Stratication factors are nodal status (cN0 vs
cN+) and study group (GBG vs IBCSG). Adequate organ functions and
a good performance status (ECOG PS 0-1) are required. Pts with a body
mass index >30, diabetes mellitus type I or uncontrolled type II, and/or
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts38
a history of BC within the last 5 years are excluded. Primary endpoint is
pathological complete response (pCR; ypT0/is ypN0) as determined by
core biopsy and/or denitive surgery. Secondary endpoints include com-
parison of other pCR denitions, invasive disease-free survival, overall
survival, and safety. Further (neo)adjuvant systemic treatment and radio-
therapy will be administered at the discretion of the investigator accord-
ing to standard of care.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
1029
Automated prognosis marker assessment in 2’004 breast
cancers using an articial intelligence-based framework for
BLEACH&STAIN mfIHC
Tim Mandelkow1; Elena Bady1; Jan H. Müller1; Nicolaus F. Debatin1;
Magalie C. J. Lurati1; Claudia Hube-Magg1; Guido Sauter1
1Martinistraße 52, Universitätsklinikum Hamburg-Eppendorf, Pathologie,
Hamburg, Deutschland
Background: Prognostic markers in routine clinical practice of breast
cancer are currently assessed using multi-gene panels. However, the
uctuating tumor purity can reduce the predictive value of such tests.
Immunohistochemistry (IHC) holds the potential for a better risk
assessment.
Methods: To enable automated prognosis marker detection (i.e. HER2,
GATA3, PR, ER, and AR, TOP2A, Ki-67, TROP2), we have developed
and validated a framework for automated breast cancer identication,
which comprises three dierent articial intelligence analysis steps and
an algorithm for cell-distance analysis of 11+1 marker BLEACH&STAIN
multiplex uorescence immunohistochemistry (mfIHC) staining in 2’004
breast cancers.
Result: e optimal distance between Myosin+ basal cells and benign
panCK+ cells was identied as 25 µm and used to exclude benign glands
from the analysis combined with several deep learning-based algorithms.
Our framework discriminated normal glands from malignant glands
with an AUC of 0.96. e accuracy of the approach was also validated by
well-characterized biological ndings, such as the identication of 13%
HER2+, 73% PR+/ER+, and 14 triple negative cases. Furthermore, the auto-
mated assessment of GATA3, PR, ER, TOP2A-LI, Ki-67-LI and TROP2
was signicantly liked to the tumor grade (p<0.001 each). A high expres-
sion level of HER2, GATA3, PR, and ER was associated with a prolonged
overall survival (p≥0.002 each).
Conclusion: A deep learning-based framework for automated breast can-
cer identication using BLEACH&STAIN mfIHC facilitates automated
prognosis marker quantication in breast cancer.
Disclosure Statement: e authors declare the following: e PR (MSVA-570R),
the AR (MSVA-367R), the ER (MSVA-564R), the TROP2 (MSVA-733R), TOPO2A
(MSVA-802R), Myosin H11 (MSVA-375R), panCK (MSVA-000R), Ki-67 (MS-
VA-267M), GATA3 (MSVA-450M), PD-L1 (MSVA-711R) antibody clone were
provided from MS Validated Antibodies GmbH (owned by a family member
ofGS).
1032
Evaluation of the Age Limits of Mammography Screening in
Germany – A Decision-Analysis to Inform Decision Making
based on Long-Term Benets and Harms
Gaby Sroczynski1; Lara Hallsson1; Nikolai Mühlberger1; Felicitas Kühne1;
Beate Jahn1,2; Heike Kölsch3; Stefan Sauerland3; Konstanze Angelescu3;
Uwe Siebert1,2,4,5
1Institute of Public Health, Medical Decision Making und Health Technology
Assessment, UMIT - University for Health Sciences, Medical Informatics and
Technology, Hall i. T., Österreich
2Division of Health Technology Assessment, ONCOTYROL Center for
Personalized Cancer Medicine, Innsbruck, Österreich
3Institute for Quality and Eciency in Health Care (IQWiG), Cologne,
Deutschland
4Center for Health Decision Science, Departments of Epidemiology and Health
Policy & Management, Harvard T. H. Chan School of Public Health, Boston, USA
5Institute for Technology Assessment and Department of Radiology,
Massachusetts General Hospital, Harvard Medical School, Boston, USA
Background: In Germany, the organized breast cancer (BC) screen-
ing program includes biennial mammography for women in the age of
50-69 years. We evaluated the long-term benets and harms of various
BC screening strategies including mammography with earlier start and/or
later stop at dierent screening intervals.
Methods: We developed a Markov-state-transition model simulating BC
progression including ductal carcinoma in situ (DCIS) to evaluate various
screening strategies diering by age at start and end of screening and by
screening interval. International data for mammography accuracy along
with German epidemiologic, clinical data and age-specic quality-of-life
(QoL) data were used. Outcomes included detected DCIS and invasive
BC, BC-related deaths, life years [LY], and quality-adjusted LY (QALY),
number of positive, false-positive, and total mammograms, overdiagnosis,
and the incremental harm-benet ratio (IHBR). Comprehensive sensitiv-
ity analyses were conducted.
Result: In the base-case analysis, the highest gain in LY was achieved
with mammography at age 45–79 (annual, age 45–49y; biennial, 50–79y)
with 10.0 LY gained [LYG] per 100 participating women compared with
current screening. e highest gain in QALYs is expected by biennial
mammography at ages 45–74 (3.5 QALYs gained/100 women vs. current
screening). Lowering the start age to 45 years (biennial, age 45–69y) has
an IHBR of 47 additional mammograms/LYG (vs. current screening).
Compared to this screening, additionally extending mammography to 74
years (biennial, age 45–74y) results in 96 additional mammograms/LYG.
Annual screening at age 45–49 or extending biennial screening to age
79 results in substantially less favorable IHBRs. Overdiagnoses occurred
mainly due to DCIS. Key results were robust in sensitivity analyses.
Conclusion: Based on our results, extension of the starting and stopping
age for mammography may prevent additional BC deaths and increase
remaining life expectancy. Considering QoL, biennial screening from age
45 to 74 years provides an acceptable benet-harm balance.
Disclosure Statement: e authors declare the following: is work was con-
ducted and funded within a benet assessment of the Institute for Quality and
Eciency in Health Care (IQWiG) commissioned by the Federal Joint Committee
(G-BA).
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 39
1059
MINERVA - Combination of Abemaciclib and endocrine
therapy in hormone receptor positive (HR+) HER2 negative
(HER2-) locally adv./metastatic breast cancer with focus on
digital side eect management
Brigitte Rack1; Natalie Uhl1; Kristina Veselinovic1; Amelie Degregorio2;
Thomas W. P. Friedl1; Kerstin Pster1; Angelina Fink1; Tanja Fehm3;
Jens Huober4; Wolfgang Janni1
1University Hospital Ulm, Department of Gynecology and Obstetrics, Ulm,
Deutschland
2SLK-Kliniken, Heilbronn, Department of Gynecology and Obstetrics, Heilbronn,
Deutschland
3Heinrich-Heine-University Düsseldorf, Department of Gynecology and
Obstetrics, Düsseldorf, Deutschland
4Kantonsspital St.Gallen, Breast Unit, St. Gallen, Schweiz
Background: Systematic collection of self-assessed Patient-Reported
Outcome (PRO) has gained increasing interest in clinical oncology.
Clinical monitoring of PROs via digital application tools oers signicant
benets. Patient reported side eects enable early intervention or treat-
ment adaption leading to reduced toxicity and increased quality of life
(QoL), as well as earlier detection of progressive disease (PD) or lack in
treatment eectiveness.
Clinical Trial Design/Methods: e MINERVA study is designed as an
open-label, non-randomized, phase IV trial to assess the ecacy and
safety of the CDK 4/6 inhibitor Abemaciclib plus endocrine therapy in
300 women with HR+HER2- advanced/metastatic breast cancer in a rst
line setting with focus on digital side eect management.
MINERVA oers a mandatory use of CANKADO Pro-React, a digital
health application to support therapy management and physician-patient
interaction. is includes a patient diary for daily documentation of can-
cer-/treatment-related symptoms as well as frequent QoL-questionnaires
(EORCT-QLQ-C30 and BR23). An integrated algorithm detects early
symptom deteriorations, triggers alert notications and gives recommen-
dations for timely symptom management. Patient-specic reports support
the preparation of patient visits and monitoring of patient compliance. A
translational research project will aim to identify markers for endocrine
treatment resistance.
e primary objective of this trial is the estimation of progression
free survival (PFS) from date of registration until PD or death. Secondary
objectives include the evaluation of adverse events and additional cap-
ture of Patient-Reported side eects on a daily basis via CANKADO
PRO-React.
Result: n/a
Discussion: n/a
Conclusion: e MINERVA study investigates the eectiveness and safety
of an endocrine-based therapy in combination with Abemaciclib with a
focus on digital side eect management and will lead to further insights
regarding safety, tolerability and QoL of this treatment regimen.
Disclosure Statement: e authors declare the following: Financial Disclosure
Cancer of Unknown Primary (CUP)
Poster
223
Baseline mutational proles of patients (pts) with carcinoma-
of-unknown-primary-origin (CUP) enrolled onto CUPISCO
Benedikt Westphalen1; Armen R. Karapetyan2; Andreas Beringer2;
Tilmann Bochtler3; Nassera Chalabi2; Natalie Cook4;
Gonzalo Duran-Pacheco2; Sophie Golding2; Elen Hoglander2; Ferran Losa5;
Linda Mileshkin6; Holger Moch7; Chantal Pauli7; Jerey S. Ross8,9;
Ethan S. Sokol8; Richard W. Tothill10; Alwin Krämer3
1Comprehensive Cancer Center Munich, Ludwig Maximilian University of
Munich, Department of Medicine III, Munich, Deutschland
2F. Homann-La Roche Ltd, Basel, Schweiz
3Deutsches Krebsforschungszentrum, Heidelberg, Deutschland
4The University of Manchester, The Christie NHS Foundation Trust, Manchester ,
Vereinigtes Königreich
5Hospital de Sant Joan Despí Moisès Broggi, ICO-Hospitalet, Barcelona, Spanien
6Peter MacCallum Cancer Centre, Melbourne, Australien
7Universitätsspital Zürich, Institut für Pathologie und Molekularpathologie,
Zürich, Schweiz
8Foundation Medicine Inc, Cambridge, USA
9SUNY Upstate Medical University, Syracuse, USA
10University of Melbourne, Department of Clinical Pathology, Parkville,
Australien
Background: NCCN guidelines consider next-generation sequencing
important in guiding therapeutic decision-making in CUP. CUPISCO
(NCT03498521) is an ongoing, phase II randomised study of targeted
therapy/cancer immunotherapy vs platinum-based chemotherapy in
pts with unfavourable CUP, dened per ESMO guidelines. We present a
descriptive molecular analysis of ~50% of pts designated for enrolment.
Methods: Comprehensive genomic proling, including determination of
microsatellite instability (MSI) and tumour mutational burden (TMB),
was performed on formalin-xed, paran-embedded tissues using the
F1CDx assay. Gene alterations (GAs) found in ≥3% of pts were analysed
using multiple correspondence analyses and hierarchical clustering to
identify co-occurrences.
Result: Median age was 61.5 years (n = 346 [Apr 2021]; range: 22–84);
median TMB was 2.5 mut/Mb (0–63.0). Most frequent GAs were TP53
(44%), CDKN2A (32%), KRAS (21%; 2% G12C), CDKN2B (21%),
ARID1A (13%), STK11 (13%), MTAP (12%), PIK3CA (10%), MYC (8%),
PBRM1 (8%), BAP1 (8%) and FGFR2 (8%). Beyond PIK3CA and FGFR2,
other targetable GAs were identied in EGFR (2%), ERBB2 (6%), ALK
(0.3%), ROS1 (1%), MET (2%), NTRK1 (1%) and BRAF (6%). e fre-
quency of MSI-high and TMB-high (>16 mutations/Mb) samples was 3%
and 9% respectively. Based on hierarchical clustering of co-mutational
proles, multiple clusters were identied, each characterised by specic
GA co-occurrences.
Discussion: In our analysis, 30% of patients carried a potentially targeta-
ble GA, shedding light on the molecular landscape in pts with poor-prog-
nosis CUP. Our analyses demonstrate that CUP cases can be clustered
based on molecular proling; further studies are needed to determine if
these clusters carry clinical relevance.
Conclusion: Our early results suggest that comprehensive genomic prol-
ing of CUP samples identies therapeutically relevant GAs in a signicant
proportion of patients and could thus guide personalised treatment.
Previously presented atESMO2021,“FPN:1804P,C. Benedikt Westphalen
et al.”Reused with permission.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts40
261
Relevance of the time interval between surgery and adjuvant
radio (chemo) therapy in HPV-negative and advanced head
and neck carcinoma of unknown primary (CUP)
Matthias Balk1; Robin Rupp1; Konstantin Mantsopoulos1; Moritz Allner1;
Philipp Grundtner1; Sarina Müller1; Maximilian Traxdorf1;
Markus Eckstein2; Stefan Speer3; Sabine Semrau3; Rainer Fietkau3;
Heinrich Iro1; Markus Hecht3; Antoniu-Oreste Gostian1
1Hals-Nasen-Ohren-Klinik, Kopf- und Halschirurgie, Friedrich-Alexander
Universität Erlangen-Nürnberg, Erlangen, Deutschland
2Pathologisches Institut, Friedrich-Alexander Universität Erlangen-Nürnberg,
Erlangen, Deutschland
3Strahlenklinik, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen,
Deutschland
Background: e eect of therapy duration in HNSCC-CUP has not
been thoroughly investigated, thus this study aimed to assess as primary
objective the impact of the time range between surgery and adjuvant ther-
apy on the oncologic outcome, in particular the overall survival (OS), in
advanced staged, HPV negative CUP at a tertiary referral hospital. Disease
specic survival (DSS) and progression free survival (PFS) are dened as
secondary objectives.
Methods: Between January 1st, 2007, and March 31st, 2020 a total of 131
CUP- patients were treated. Out of these, 59 patients with a conrmed
negative p16 analysis were referred to a CUP-panendoscopy with simulta-
neous unilateral neck dissection followed by adjuvant therapy. e cut-o
between tumor removal and delivery of adjuvant therapy was set at the
median of 55 days (d; 95% CI 51,42-84,52), i.e. 30 patients received adju-
vant therapy within 55 d (mean 41.69 d, SD=9.03) aer surgery in contrast
to 29 patients at least aer 55 d (mean 73.21 d, SD=19.16).
Result: e mean follow-up time was 43.6 months (SD=36.7 months).
Regarding all patients, the OS was 71% (95% CI 0.55-0.86). Patients
receiving adjuvant therapy < 55 d (77%, 95% CI 0.48-1.06) had compara-
ble OS compared to those ≥ 55 d (64%, 95% CI 0.42-0.80; X2(1) =1.16, p =
0.281). e DSS of all patients was 86% (95% CI 0.75-0.96). For the group
< 55 d it was 95% (95% CI 0.89-1.01) compared to the group ≥ 55 d with
76% (95% CI 0.57-0.95; X2(1) =2.32, p = 0.128). e PFS was 72% (95% CI
0.59-0.85). In the group < 55 d it was 78% (95% CI 0.63-0.94) and thus not
signicantly dierent from 65% (95% CI 0.45-0.85) of the group ≥ 55 d;
X2(1) =0.29, p = 0.589).
Conclusion: e results presented suggest that the oncologic outcome of
patients with advanced, HPV-negative HNSCC-CUP is not aected by
an extended time between surgery and adjuvant therapy. Consequently,
patients with advanced CUP may still benet from delayed adjuvant
therapy.
Disclosure Statement: e authors declare no conict of interest.
Cancer Prevention
Best-of-Abstract-Vortrag
102
HaSCo Study: First results of a pilot study for systematic
HPV self-sampling for non-responders to the cervical cancer
screening program
Matthias Jentschke1; Sophia Groß1; Stephanie Hempel1;
Lena Steinkasserer1; Barbara Neuhaus2; Siegfried Geyer3; Armin Koch4;
Peter Hillemanns1
1Klinik für Frauenheilkunde und Geburtshilfe, Medizinische Hochschule
Hannover, Hannover, Deutschland
2Zentrum für klinische Studien, Medizinische Hochschule Hannover, Hannover,
Deutschland
3Medizinische Soziologie, Medizinische Hochschule Hannover, Hannover,
Deutschland
4Institut für Biometrie, Medizinische Hochschule Hannover, Hannover,
Deutschland
Background: In this pilot study we evaluate a systematic approach
towards human papillomavirus (HPV) self-sampling for non-responders
to the German cervical cancer screening program. In 2020, the renewed
organized screening program with co-testing (HPV test + cytology) in
3-yearly intervals was started for all women 35 years and older. In the past,
the participation rate was around 70% in a time frame of three years. e
non-participators are at higher risk to develop invasive cervical cancer.
e willingness to participate can be improved by oering self-sampling
devices for home-based use. Based on this information, the Hannover
Self-Collection study was started to examine the response rate and practi-
cability of a systematic self-sampling approach.
Methods: 20.000 women aged 30 to 65 years living in the city and region
of Hannover, Lower Saxony were randomly included. 10.000 women
directly received a self-sampling kit, the other 10.000 a letter of informa-
tion and option to participate in the study (opt-out vs. opt-in strategy).
Stratications were be made by age (7 cohorts) and area of living (city vs
rural). Women tested positive for high-risk HPV (PCR-based HPV assay)
were prompted to get a cytological smear by their gynecologist. Women
with normal cytology will be re-checked aer 6 months. Suspicious cytol-
ogy results lead to an immediate colposcopy.
Results: e study is executed between December 2021 and May 2022.
First results will be presented at the congress.
Discussion and Conclusions: To get hold of non-responders to cervical
cancer screening programs, self-sampling for HPV is a promising option.
Aim of this study is to generate an overall recommendation to improve
cervical cancer screening in Germany, especially for non-responders. is
study is supported by Deutsche Krebshilfe.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 41
852
A Randomized Trial of Risk-Adapted Screening for Prostate
Cancer in Young Men – Updated Results of the First Screening
Round of the PROBASE Trial
Peter Albers1,2; Christian Arsov1,3; Jale Lakes1; Jan Philipp Radtke1;
Kathleen Herkommer4; Jürgen Gschwend4; Inga Peters5; Markus Kuczyk5;
Stefan Koerber6; Jürgen Peter Debus6; Boris Hadaschik7; Glen Kristiansen8;
Lars Schimmöller9; Gerald Antoch9; Ernst Rummeny10; Marcus Makowski10;
Frank Wacker11; Heinz Schlemmer12; Axel Benner13; Roswitha Siener14;
Rudolf Kaaks15; Nikolaus Becker16
1Department of Urology, Medical Faculty, Heinrich-Heine University Düsseldorf,
Düsseldorf, Deutschland
2Division of Personalized Early Detection of Prostate Cancer, German Cancer
Research Center (DKFZ), Heidelberg, Deutschland
3Department of Urology, Städtische Kliniken Mönchengladbach,
Mönchengladbach, Deutschland
4Department of Urology, Technical University Munich, Deutschland
5Department of Urology, Medical University Hannover (MHH), Hannover,
Deutschland
6Department of Radiooncology, University Hospital Heidelberg, Heidelberg,
Deutschland
7Department of Urology, University Hospital Essen, Essen, Deutschland
8Department of Pathology, University Hospital Bonn, Bonn, Deutschland
9Institute of Diagnostic and Interventional Radiology, University Hospital
Düsseldorf, Department of Urology, Düsseldorf, Deutschland
10Institute of Radiology, Technical University Munich, München, Deutschland
11Institute of Radiology, Medical University Hannover (MHH), Hannover,
Deutschland
12Institute of Radiology, German Cancer Research Center (DKFZ), Heidelberg,
Deutschland
13Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg,
Deutschland
14Department of Urology, University Hospital Bonn, Bonn, Deutschland
15Division of Cancer Epidemiology, German Cancer Research Center (DKFZ),
Heidelberg, Deutschland
16Division of Personalized Early Detection of Prostate Cancer, German Cancer
Research Center (DKFZ), Heidelberg, Deutschland
Background: Prostate-specic antigen (PSA) – based screening has
proven to signicantly reduce prostate cancer (PCa) mortality. However,
population-based screening for PCa suers from a high rate of overdiag-
nosis followed by overtreatment. A digital rectal examination (DRE) still
represents the mainstay of the German statutory early detection program.
In contrast, risk-adapted approaches have been suggested to improve the
accuracy. Here we report on updated results of the risk-adapted PROBASE
screening trial for PCa aer the rst screening round.
Methods and Participants: From February 2014 to December 2019,
PROBASE recruited and randomized 46,642 men in Germany at age 45
to receive either an immediate PSA test (arm A) or a delayed PSA test at
age 50 (arm B). Participants in arm B were oered a DRE at the time of
enrolment instead of a PSA test. PSA tests classied participants in arm A
into a low (<1.5 ng/ml), intermediate (1.5-2.99 ng/ml) or high (>3 ng/ml)
risk category. In cases of conrmed PSA values >3 ng/ml participants were
recommended a prostate biopsy based on upfront multiparametric mag-
netic resonance imaging.
Results: Baseline PSA tests categorized the 23,301 participants of arm
A into low (89.2%) and intermediate (9.3%) risk. With conrmed PSA
>3ng/ml 186 (0.8%) men were at high risk of whom 120 (64.5%) under-
went a biopsy with detection of 48 prostate cancers (overall prevalence
0.2%). Only four patients had International Society of Uropathology
(ISUP) grade group (GG) > 3 cancers (overall prevalence 0.02%). In arm
B, 23,194 participants were enrolled and 6,537 underwent a DRE with 57
suspicious ndings. Two of which showed ISUP GG 1 PCa corresponding
to a detection rate by DRE of 0.03% (2/6,537).
Discussion and Conclusion: e majority of men (about 90%) at age 45
presents with a PSA below 1.5 ng/mg which implies a very low risk to
develop prostate cancer. e prevalence of screen-detected clinically sig-
nicant PCa in 45-year-old men is very low. Moreover, the rate of aggres-
sive cancers (ISUP GG 3-5) is even lower. DRE did not turn out eective
for early detection of PCa.
Disclosure Statement: e authors declare no conict of interest.
Poster
451
Changes in modiable life style factors in women
with an increased hereditary risk for breast and ovarian
cancer during the SARS-CoV-2 pandemic in Germany:
A cross-sectional web-based survey
Roxana Schwab; Annika Droste; Annette Hasenburg
University Medical Center Mainz, Department of Gynecology and Obstetrics,
Mainz, Deutschland
Background: Pathogenic mutations in BRCA1 and BRCA2 are associated
with high risks of breast (BC) and ovarian cancer (OC). Modiable life
style factors are important in explaining some of the variation in cancer
risks in both, OC and BC. Crucial steps to prevent malignant disease are
increased physical activity, avoidance of smoking, limitation of the intake
of red meat or alcohol.
Methods: To assess possible changes in life style, a web-based survey was
placed on internet platforms of patients´ support groups between 29th
January and 22th April 2021. Missing data were composed of those patients
who did not answer the question or who did not have a clear opinion
regarding the topic. Data are presented as frequencies of selected items.
Group dierences were calculated by χ2-test.
Result: During the pandemic, 10.5% of respondents consumed signi-
cantly more or more alcohol, while 31.6% consumed less or signicantly
less alcohol than before the pandemic. With respect to abuse of nico-
tine, 11.8% consumed more and 17.6% consumed less than before the
pandemic. 16.2% engaged in signicantly more or more physical activ-
ity, whereas 47.1% engaged in less or signicantly less physical activity,
respectively. 8.7% stated that they maintained a healthy body weight,
while 17.4% did not. A healthy diet was strictly observed or observed by
13.9% of respondents, while 23.6% observed a healthy diet less or signi-
cantly less than before the pandemic.
Discussion: e exact impact of life style changes during the SARS-CoV-2
pandemic on cancer (recurrence) risk, as well as on subsequent survival,
is still unknown, but it has the potential to lead to important public health
implications in the coming years.
Conclusion: us, especially during challenging periods of life, women
at high risk for cancer occurrence or recurrence should be reassured that
observing a healthy lifestyle (healthy diet, control of obesity, decreased
smoking etc.) is an excellent option for cancer prevention and increased
survival.
Disclosure Statement: e authors declare the following:
RS: Honoraria: Roche Pharma AG, AstraZeneca, Streamedup!GmbH AH: Hono-
raria: AstraZeneca; Celgen; MedConcept GmbH, Med update GmbH; Medicultus;
Pzer; Promedicis GmbH; Soconsult; Roche Pharma AG; Streamedup!GmbH;
Tesaro Bio Germany GmbH, LEO Pharma Ad Board: PharmaMar; Promedicis
GmbH; Roche Pharma AG; Tesaro Bio Germany GmbH, AstraZeneca, LEO
Pharma, MSD Sharp & Dohme GmbH
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts42
570
Impact of a German campaign promoting physical activity
against cancer on physical activity levels
Dimitra Theoklitou; Freerk T. Baumann
Uniklinik Köln, Klinik I für Innere Medizin, Centrum für Integrierte Onkologie
Aachen Bonn Köln Düsseldorf, Köln, Deutschland
Abstract: Purpose: e instrumental role of physical activity in the pri-
mary prevention of cancer is indisputable. e current study aimed
to evaluate the success of the information campaign “Physical activity
against cancer” in Germany.
Methods: A total of 2,003 telephone interviews were conducted using two
telephone surveys (September 2013, n=1,000; September 2014, n=1,003)
among randomly chosen participants aged 18 years or older using the
Global Physical Activity Questionnaire (GPAQ). Questions aimed at
assessing the accessibility of the campaign and its impact on physical
activity levels and the knowledge of the participants regarding the relation
between physical activity and cancer prevention.
Results: Results showed that 27% of participants of the second survey had
heard about the campaign. e metabolic equivalent task (MET) scores
in total and for the physical activity from transportation for those who
were exposed to the information compared to the rest interviewees were
associated with statistically signicant eects.
Discussion: e campaign “Physical activity against cancer” had a suc-
cessful impact on the increment of the physical activity levels of the par-
ticipants who were exposed to the information of the campaign and can
be considered as a motivator for people to become physically more active.
According to the results of both surveys, there is an excess of knowledge
among the respondents that regular physical activity can have an impact
on the cancer risk reduction, which can play an important role in cancer
prevention.
Conclusions: Information campaigns and education can have an inu-
ence on changing peoples movement behavior. e question remains
whether these observations are possibly associated with cancer in partic-
ular and are therefore dicult to transfer to other diseases. Methodical
limitations were that this was a cross sectional study and the missing con-
trolled intervention exercise program.
Disclosure Statement: e authors declare no conict of interest.
724
Pilot project: Easily said and done: Prevention and early
detection of colon cancer and skin cancer
Sandra Bothur1; Inga Knapp2; Friederike Kreuzwieser1; Martin Schieron3;
Tanja Segmüller3
1Krebsgesellschaft Nordrhein-Westfalen e.V., Düsseldorf, Deutschland
2Kompetenzzentrum Barrierefreiheit Volmarstein, Wetter (Ruhr), Deutschland
3HS Gesundheit Bochum - Hochschule für Gesundheit, Department of
Community Health, Bochum, Deutschland
Background: Colon cancer is the second most common cancer in women
and third most common in men in Germany - black skin cancer is the
fourth most common cancer in women and h in men. Studies show
that persons with so-called intellectual disabilities use cancer screening
programs less than the average population. It can be assumed that the
usual information material on cancer prevention and care do not reach
these persons adequately.
Methods: e information must be made available and disseminated in
such a way that it reaches the target audience. e project takes a partici-
patory approach, involves various stakeholders and asks people from the
target group themselves about their information needs and ways of obtain-
ing information. e content was developed in focus groups and surveys
of the target groups on image and training design were implemented.
Result: Easy to read language can help to achieve accessible communi-
cation for people with learning diculties. is refers to both written
information (e.g. information brochures) and oral communication (e.g.
conversation with a doctor). Self-determination and participation can
only succeed if information reaches the person. is means: All the nec-
essary information must be available and conveyed in easy language.
Analogue and digital media were developed in a participatory manner to
support doctor-patient-communication.
Discussion: Overall, these persons have diverse, multifaceted problems
with health care. For example, in many cases individual initiative and
responsibility is necessary to participate in an examination. is is not
always the case for people with so-called intellectual disabilities. eir
previous experiences in the health sector and the relationship with the
doctor, which can oen be disturbed by communication diculties, also
play an important role.
Conclusion: e project is an important contribution to improving health
communication for people with so-called learning diculties and medical
professionals.
Disclosure Statement: e authors declare no conict of interest.
940
Evaluation of HPV-vaccination campaigns in Germany: Reach
of target groups and impact on vaccine uptake willingness
Catharina Maulbecker-Armstrong1; Karin Moser1; Nobila Ouedraogo2
1Fachbereich Gesundheit, Technische Hochschule Mittelhessen, Gießen,
Deutschland
2Deutsches Krebsforschungszentrum, Krebsprävention, Heidelberg,
Deutschland
Background: German population is poorly informed about the HPV-
vaccination and its health benets. is is shown by the low vaccination
rates (2019: girls 47.2%, boys 5.1%). Despite educational information pro-
vided by German Federal Centre for Health Education (BZgA) over years,
progress in HPV-vaccination rate is still low. us, existing communica-
tion strategies on HPV-vaccination need to be evaluated and adapted if
necessary.
Methods: We aim to evaluate a nation-wide HPV campaign planned by
the manufacturer of the HPV vaccine Gardasil with regards on the reach
of the target groups (parents, teens, students) and the impact on vaccine
uptake willingness. Surveys will be carried out in the target groups for
this purpose. In this work a rst survey with parents from children in
class 3 to 6 is planned and a second one for adolescents at the age of 15-16
years. A third survey will be performed among students of the Technische
Hochschule Mittelhessen (THM). In all cases we want to analyze how
informed the respective group is, if they are vaccinated or if they are will-
ing to get vaccinated themselves or in the case of the parents to let their
children be vaccinated.
Result: We expect an increase in HPV-vaccination uptake or in willing-
ness to get vaccinated among target groups exposed to the campaign and
to learn about additional alternate communication channels.
Discussion: To increase the HPV-vaccination rate, it is crucial to ade-
quately inform the population. Parents and adolescents can decide and
act appropriately only if they are aware of the risk of an HPV-infection.
Information can happen through campaigns, by pediatricians, family
doctors and through events at schools. Classic communication channels
are not as attractive for adolescents. To reach them, their channels (e.g.
opinion-vlogger or YouTuber as role models) have to be used. Vaccination
rates can only increase if all target groups are both reached through their
respective Channels and informed.
In collaboration with the Allianz gegen HPV
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 43
941
Lost cohorts in the HPV vaccination due to the covid-19
pandemic and potential eects on future HPV associated
cancers
Catharina Maulbecker-Armstrong1; Karin Moser1; Nobila Ouedraogo2
1Fachbereich Gesundheit, Technische Hochschule Mittelhessen, Gießen,
Deutschland
2Deutsches Krebsforschungszentrum, Krebsprävention, Heidelberg,
Deutschland
Background: Due to covid-19 pandemic, the lock downs and long home-
schooling periods children /adolescents and their parents were neither
reachable for school personnel nor for healthcare professionals. erefore,
vaccination rates decreased by 14% for girls and 9% for boys (DAK Kinder-
und Jugendreport 2021). Consequently, children in the target age of 9 to
14 years were lost for the HPV-vaccination. A 2-dose-vaccination-scheme
is used for children younger than 15 years. Older kids need 3 vaccinations
for a complete immunization. e GKV generally reimburses only the
cost for age groups younger than 18 years. We aim to assess the resulting
HPV associated treatment cost in the German healthcare system and to
develop a proposal on how to get the lost cohorts vaccinated.
Methods: To assess the additional cost related to the decrease in vacci-
nation rates, we plan to use the following approaches: Scenarios analysis
of the need of the 3-dose-scheme (Vaccine, organization, personnel) and
future HPV related treatment costs. We will conduct expert interviews
and compare sales gures of Gardasil with data from the KV. Finally, we
compare European / international countries, on how do they organize the
catch-up for the lost cohorts.
Result: We expect increasing costs due to a third vaccination regime and
the treatment of HPV related cancers based on missing immunizations in
the juvenile age.
Discussion: An increased nancial burden will be result in the future, if
Germany fails to catch-up the lost children and adolescents based on the
HPV vaccination gap due to the pandemic. Mechanisms need to be in
place to include adolescents, i.e. through the J1-exami, for the catch-up
vaccinations. Alternatively, the age limit for a reimbursement could be
raised for a limited period of time to immunize the young adults between
18 and 20 years.
In collaboration with the Allianz gegen HPV
Disclosure Statement: e authors declare no conict of interest.
975
The role of tobacco smoking in the ecacy of brief alcohol
intervention: Results from a randomized controlled trial
Filipa Krolo1,2; Sophie Baumann3; Anika Tiede1,2; Kristian Krause1;
Christian Meyer2,4; Gallus Bischof5; Ulrich John2,4; Beate Gärtner6;
Jennis Freyer-Adam1,2
1Institut für Medizinische Psychologie, Universitätsmedizin Greifswald,
Greifswald, Deutschland
2Deutsches Zentrum für Herz-Kreislauf-Forschung, Standort Greifswald,
Greifswald, Deutschland
3Institut für Präventionsforschung und Sozialmedizin, Universitätsmedizin
Greifswald, Abteilung für Methoden der Community Medicine, Greifswald,
Deutschland
4Institut für Präventionsforschung und Sozialmedizin, Universitätsmedizin
Greifswald, Institut für Community Medicine, Greifswald, Deutschland
5Klinik für Psychiatrie und Psychotherapie, Universität Lübeck, Lübeck,
Deutschland
6Robert-Koch-Institut Berlin, Abteilung für Epidemiologie und
Gesundheitsmonitoring, Berlin, Deutschland
Purpose: Tobacco smoking and at-risk alcohol consumption are among
the most important modiable risk factors for cancer morbidity and
-mortality. is study investigated whether current tobacco smoking
moderates the ecacy and the comparative ecacy of in-person and
computer-based brief alcohol interventions in at-risk alcohol drinking
general hospital patients.
Methods: As part of a randomized controlled trial funded by Deutsche
Krebshilfe, 961 general hospital patients aged 18-64 years, were allocated
to in-person counseling (PE), computer-generated individual feedback
(CO) and assessment only. PE and CO included contacts at baseline, 1
and 3 months later. Aer 6, 12, 18 and 24 months, self-reported reduc-
tion of alcohol use per day was assessed as outcome. Using latent growth
curve models, self-reported current smoking status (yes/ no) and number
of cigarettes per day were tested as moderators of brief alcohol interven-
tion ecacy.
Results: In PE and CO, study participants reduced their alcohol use inde-
pendently of their smoking status over 24 months (ps <0.005). At month
24, neither smoking status nor number of cigarettes per day moderated the
ecacy and the comparative of PE and CO (ps >0.05). Up to month 12,
and among persons smoking 19 cigarettes per day or less, ecacy of CO
increased signicantly with increasing number of cigarettes (ps <0.05).
Discussion: Although in the short-term, heavier smokers with a maxi-
mum of 19 cigarettes per day, might benet more from CO relative to
assessment only than light smokers, smoking status and heaviness of
smoking did not interfere with intervention ecacy in the long-term.
Conclusion: For the purpose of screening and brief alcohol intervention
in medical practice, our ndings indicate that tobacco smoking does not
interfere with the ecacy of brief alcohol interventions, whether delivered
in-person or computer-based.
Disclosure Statement: e authors declare no conict of interest.
1022
Proactive Automatized Lifestyle intervention for cancer
prevention (PAL) and reach of general hospital patients
Jennis Freyer-Adam1; Marie Spielmann1; Filipa Krolo1; Anika Tiede1;
Kornelia Sadewasser1,2; Christian Meyer3; Gallus Bischof4; Ulrich John3
1Institut für Medizinische Psychologie, Universitätsmedizin Greifswald,
Greifswald, Deutschland
2Deutsches Zentrum für Herzkreislauorschung, Greifswald, Deutschland
3Institut für Präventionsforschung und Sozialmedizin, Universitätsmedizin
Greifswald, Greifswald, Deutschland
4Abteilung für Psychiatrie und Psychotherapie, Medizinische Universität zu
Lübeck, Lübeck, Deutschland
Purpose: Multiple health risk behaviors (HRBs, i.e. tobacco smoking,
at-risk alcohol use, physical inactivity and unhealthy diet) more than dou-
ble the risk of cancer, and apply to more than half of the adult popula-
tion. Targeting multiple HRBs should be in the focus of cancer prevention
research. Furthermore, preventive measures oen fail to reach the major-
ity of people and particularly those most in need and hard to reach, e.g.
with low level of school. Electronic interventions may help to eciently
address multiple HRBs in health care patients. e aim is to introduce the
Proactive Automatized Lifestyle intervention for cancer prevention (PAL)
and to report on how well general hospital patients are reached.
Methods: As part of a study funded by Deutsche Krebshilfe (70113382),
over two months (05-07/2022), all 18- to 64-year old patients admitted to
internal medicine, general surgery, trauma surgery and ear-nose-throat
medicine wards of the University Medicine Hospital Greifswald are sys-
tematically approached and invited to participate in a pre-post-interven-
tion study, irrespective of reason for admission and HRB prole. Based
on psychological behavior change theory, participants (n=175) receive
individualized computer-generated feedback aer baseline and 1 and
3 months later. Reach will be determined by the proportion of partici-
pants among eligible patients. Dierences in reach will be measured with
regards to school education.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts44
Result: To ensure individualization of feedback, a pool of >4000 text
segments, graphics and selection rules has been developed or modied
from previous single behavior interventions. Findings on reach will be
presented.
Discussion: is study is the rst to investigate the reach of a proactive,
electronic and brief multiple behavior change intervention among general
hospital patients.
Conclusions: If reach is high and ecacy established by a randomized
controlled trial, such interventions have potential for the primary and sec-
ondary prevention of cancer diseases.
Disclosure Statement: e authors declare no conict of interest.
Central Nervous System Tumors
Poster
43
Identication of senolytic agents for sequential treatment of
glioblastoma with temozolomide
Lea Beltzig; Björn Stratenwerth; Markus Christmann; Bernd Kaina
Institute for Toxicology, University Medical Center, Mainz, Deutschland
First-line therapeutic for brain cancer, glioblastoma multiforme (GBM),
is the DNA methylating drug temozolomide (TMZ). It was shown that
TMZ induces autophagy, apoptosis, low level of necroptosis and cellular
senescence (CSEN). We proposed the hypothesis that CSEN is irreversible
and GBM cells may escape from CSEN, giving rise to recurrent tumors.
erefore, treatments that specically target senescent cells, i.e. senolytic
drugs, may lead to a better outome of GBM therapy, by preventing recur-
rences. Here, we tested three natural substances, artesunate, curcumin and
setin, ionising radiation (IR) and, as positive control, a well-known seno-
lytic drug (ABT-737) for their senolytic capacity in GBM cells. Also, sev-
eral proteins involved in the DNA damage response (DDR), ATM, ATR,
pChk1/2, p53, p21, Nf-κB, Rad51, PARP, IAPs and autophagy, a pathway
involved in CSEN induction, were tested for their importance in maintain-
ing CSEN. Treatment of GBM cells with 50 µM TMZ and post-incubated
for 8 days resulted in ~80% CSEN and ~20 % apoptosis, indicatig CSEN
is the major trait induced by TMZ. To identify senolytics, we treated the
senescent population with the compounds of interest and measured the
eect on proliferating and senescent cells. e substances and IR were
used in doses non-toxic on proliferating cells. We show that artesunate,
chloroquine and setine exhibit senolytic activity, killing senescent cells
more eciently than proliferating cells. Curcumin showed the opposite
eect. Although inhibition of ATM, ATR and p53 via pithin-α led to a
decrease in CSEN, indicating their involvement in maintananing CSEN,
no increase in cell death was observed. Obviously, the corresponding inhi-
bitiors do not have senolytic activity. No eect on CSEN was observed by
inhibition of Chk1/Chk2, p21, NF-κB, Rad51, PARP and p53 by pithinµ.
We conclude that these DDR players (except p53) neither play a critical
role in maintaining TMZ-induced CSEN nor can their inhibitors be con-
sidered as senolytics. Since IR did not reduce CSEN, radiotherapy is not
designed to reduce the senescence level.
Disclosure Statement: e authors declare no conict of interest.
52
Cytotoxic and Senolytic Eects of Methadone in Combination
with Temozolomide in Glioblastoma Cells
Bernd Kaina1; Lea Beltzig1; Andrea Piee-Staa1; Bodo Haas2
1Institute for Toxicology, University Medical Center, Mainz, Deutschland,
2Federal Institute for Drugs and Medical Devices, Bonn, Deutschland
Methadone (MTD), an analgesic drug used for heroin substitution and
pain management, has recently been proposed to be benecial in can-
cer therapy. In vitro Experiments on the most common and severe brain
tumour, glioblastoma multiforme (GBM), treated with doxorubicin and
MTD showed promising results. Since, doxorubicin is not the rst line
treatment for GBM, we sought to determine the eects of the combinato-
rial treatment of MTD with the rst line treatment of GBM, temozolomide
(TMZ). erefore, a human GBM and a human broblast cell line (LN229
and VH10T) were treated with MTD and TMZ alone or in combination,
and induction of cell death and senescence, measured by annexin-V/PI
and c12FDG staining, respectively, were compared. Also, the senolytic
capacity of MTD was analysed. erefore, senescence in MTD treated and
untreated senescent cell was compared.
Treatment of LN229 and VH10T with MTD induced signicant lev-
els of apoptosis und necrosis, starting at a concentration of 20 µg/ml.
Pre-treatment of the cells with Naloxone, a competitive opioid receptor
(OR) inhibitor, did not attenuate this eect, showing its independency of
the opioid receptor. Concurrent treatment of TMZ and non-toxic con-
centration of MTD had no impact on MTD or TMZ-induced cell death.
However, an additive eect of the combinatorial treatment of TMZ with
toxic concentration of MTD (20 µg/ml) was observed. Comet and yH2AX
assays revealed that MTD is not a genotoxic agent. MTD did not induce
senescence, nor did it inuence TMZ induced senescence and despite its
cytotoxic eect on senescent cells, it cannot be considered a senolytic drug
since cytotoxicity was not exclusive to senescent cells.
In conclusion, our data revealed that MTD is cytotoxic on GBM
cell lines in concentrations above the levels reached in vivo. No syner-
gistic eect on cell death or senescence induction by concomitant TMZ
and MTD treatment was observed. Additionally, MTD has no senolytic
capacity. Although a benecial eect of MTD with doxorubicin has been
reported, our data suggest that MTD treatment does not support TMZ
based GBM therapy.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 45
53
Molecular dosimetry of temozolomide: Quantication of
critical lesions, correlation to cell death responses and
threshold doses
Björn Stratenwerth1; Susanne Geisen2; Yang He1; Lea Beltzig1;
Shana Sturla2; Bernd Kaina1
1Institute for Toxicology, University Medical Center, Mainz, Deutschland
2Department of Health Sciences and Technology, ETH Zürich, Zürich, Schweiz
Temozolomide (TMZ), the rst line treatment for glioblastoma multi-
forme (GBM), induces several alkylating adducts at N- and O-sites of the
DNA, including O6methylguanine (O6MeG). Despite being a minor lesion,
accounting for only 7 % of adducts induced by TMZ, O6MeG is responsible
for almost all genotoxic, cytotoxic, and cytostatic eects caused by TMZ.
O6MeG is repaired by the suicide enzyme MGMT. However, about 40 % of
GBM lack MGMT due to silencing of the gene by promoter methylation.
If not repaired by MGMT, O6MeG lesions provoke futile miss-match-re-
pair cycles resulting nally in DNA double strand breaks (DSBs) in can-
cer cells. How many O6MeG adducts are required to induce specic cell
responses is unknown. erefore, we aimed at determining the dose-de-
pendent formation of O6MeG and set it in relation to DSBs, p53Ser15
phosphorylation, apoptosis/necrosis and cellular senescence. Our results
indicate a linear increase of O6MeG, along with DSBs and p53Ser15 phos-
phorylation. Apoptosis/necrosis and senescence also increased linearly,
with senescence being the main response induced. A possible threshold
for the induction of apoptosis in A172 was indicated by the Hockey-stick
model at a concentration of 2.5 µM TMZ, while no threshold was detected
in LN229 cells. No threshold was detected for senescence. For A172 cells,
treatment with 20 µM TMZ induced 14.000 O6MeG adducts and 32 DSBs,
measured as yH2AX foci, leading to 12 % cell death and 35 % senescence.
Whereas in LN229 cells, 20 µM of TMZ induced 20.600 O6MeG adducts,
66 DSBs, 24 % cell death and 52 % senescence. is data translated to
the therapeutic situation indicate that intra-tumoral concentrations of
TMZ very likely trigger a signicant amount of cytotoxic and cytostatic
cell responses. is notion is further supported by an accumulation of
cytotoxic responses in a low dose repeated treatment protocol. e low
benecial properties of TMZ might result from the low rate of cell death
compared to senescence. Since TMZ/O6MeG responses require prolifer-
ation, senescent cells inevitably escape the cytotoxic eects of the drug.
Disclosure Statement: e authors declare no conict of interest.
140
Human bone marrow-derived mesenchymal stromal cells
increase glioblastoma radioresistance
Maren Strack1,2; Alexander Rühle1,2; Dieter Henrik Heiland3; Oliver Schnell3;
Anca-L. Grosu1,2; Nils Henrik Nicolay1,2
1Klinik für Strahlenheilkunde, Universitätsklinikum Freiburg, Freiburg im
Breisgau, Deutschland,
2Deutsches Konsortium für Translationale Krebsforschung (DKTK),
Partnerstandort Freiburg, Deutsches Krebsforschungszentrum (DKFZ),
Heidelberg, Deutschland,
3Klinik für Neurochirurgie, Universitätsklinikum Freiburg, Freiburg im Breisgau,
Deutschland
Background: Previous studies have shown that the number of tumor-in-
ltrating mesenchymal stromal cells (MSCs) inversely correlates with the
survival of glioblastoma (GBM) patients, providing a rationale to examine
whether MSCs causally contribute to the poor radiation response of glio-
blastoma cells (GBCs).
Methods: e immortalized cell line U251 and two primary GBCs, iso-
lated from surgical samples of a primary and a recurrent GBM, were
co-cultured with human bone-marrow derived MSCs from three dier-
ent donors. Colony forming, proliferation and metabolic viability assays
were performed to analyze the inuence of MSCs on the radiosensitivity
of GBCs. A modied Boyden Chamber migration assay was used to
examine the eect of radiotherapy on GBCs’ ability to attract MSCs
chemotactically.
Cell cycle distribution and apoptosis rates were quantied by ow
cytometry, while the expression of the radioresistance-related Growth
Associated Protein 43 (GAP43) was studied based on immunuorescene
stainings.
Result: Direct MSC co-culture increased GSCs’ clonogenic survival and
proliferation aer irradiation, whereas MSC-conditioned medium did not
aect GBCs’ metabolic activity. e number of MSCs migrating towards
primary GBCs decreased aer irradiation of GBCs, suggesting reduced
release of chemotactic factors by GBCs. Presence of MSCs caused a pro-
nounced G2/M phase arrest and reduced apoptosis rates in primary GBCs
aer irradiation. GAP43 expression in GBCs was considerably enhanced
when co-cultured with MSCs.
Discussion: Bone marrow-derived MSCs exert radioprotective eects
on GBCs which could partly explain the pro-tumorigenic eect of
tumor-inltrating MSCs in glioblastoma patients. As co-culturing with
MSCs increases the expression of GAP43 in GBCs, we established an siR-
NA-based knockdown to analyze whether GAP43 silencing can mitigate
MSCs’ radioprotective eects.
Conclusion: Bone-marrow derived MSCs increase the radioresistance of
GBCs in vitro.
Disclosure Statement: e authors declare no conict of interest.
254
Quality of life of patients with newly diagnosed glioblastoma
during TTFields therapy in routine clinical care: rst results of
the TIGER study
Oliver Bähr1; Ghazaleh Tabatabai2; Rainer Fietkau3; Roland Goldbrunner4;
Martin Glas5,6
1General Hospital Aschaenburg-Alzenau, Department of Neurology,
Aschaenburg, Deutschland
2University Hospital Tuebingen, Department of Neurology and Interdisciplinary
Neurooncology, Tübingen, Deutschland
3University Hospital Erlangen, Department of Radiation Oncology, Erlangen,
Deutschland
4University Hospital Cologne, Center for Neurosurgery, Köln, Deutschland
5University Hospital Essen, University Duisburg-Essen, Division of Clinical
Neurooncology, Department of Neurology, Essen, Deutschland
6University Hospital Essen, University Duisburg-Essen, West German Cancer
Center (WTZ) and German Cancer Consortium Partner Site, Essen, Deutschland
Background: Glioblastoma (GBM) is an aggressive primary tumor of the
central nervous system. Current treatment strategies include maximal safe
resection, followed by treatment with radiation and an alkylating chemo-
therapy. Based on the positive phase 3 trial EF-14, the addition of Tumor
Treating Fields (TTFields) to temozolomide (TMZ) maintenance therapy
brought an additional treatment method to clinical routine. e TIGER
(TTFields In GErmany in Routine Clinical Care) study documents the use
of TTFields in routine clinical care focusing on health-related quality of
life (HRQoL), treatment compliance and duration.
Methods: is multi-center prospective non-interventional study in
Germany (NCT03258021) included ndGBM patients eligible for TTFields
therapy. Following their consent to participate in the study, patients
received a comprehensive introduction to the therapy and their baseline
(BL) demographic data were collected. Information on TTFields ther-
apy decision is evaluated based on a dedicated TTFields questionnaire at
BL in both arms, follow-up information on how patients cope with the
therapy is collected 2 months aer TTFields treatment start, if applicable.
HRQoL was assessed in patients deciding for TTFields therapy at BL as
well as at 2 and 4 months thereaer using the EORTC-QLQ-C30/BN-20
questionnaires.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts46
Result: Between August 2017 and November 2019, 710 patients (259
female/451 male) were enrolled at 81 centers. e mean age was 58.5
years (range: 19.0-85.0). e overall BL characteristics of the study group
reects a typical GBM population. 582 (82%) decided to start TTFields
and 128 (18%) refused TTFields treatment. HRQoL did not decline
during TTFields therapy except for itchy skin, comparable to the results
of the EF-14 phase 3 trial. A detailed analysis of the cohort as well as their
reported QoL will be presented.
Conclusion: e TIGER study is the largest non-interventional trial on
the use of TTFields in routine clinical care. e use of TTFields in patients
with ndGBM did not impair HRQoL during the follow-up period, except
for more itchy skin.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
275
Intracranial metastases from prostate cancer - Retrospective
analysis of a clinical cohort study
Fortesa Bytyqi; Sebastian Thomas; Cornelia Cedzich; Jan Walter
Klinikum Saarbrücken , Neurochirurgie, Saarbrücken, Deutschland
Objective: Cerebral metastases arising from prostate cancer have been
described in literature rarely and poorly. e aim of this study is to pres-
ent the epidemiology, diagnostic regime, clinical presentation, therapeutic
strategies and prognosis of intracranial metastatic prostate cancer patients.
Methods: Single center retrospective meta-analysis of a clinical cohort
study including patients with prostate cancer that have been hospitalized
between 2008 and 2018. Clinical presentation was classied using the
National Institutes of Health Stroke Scale (NIHSS) and outcome was mea-
sured by the modied Rankin Scale (mRS).
Results: Out of 2450 patients with prostate cancer, 8 cases with intracra-
nial metastases were identied. In three patients the diagnosis could be
veried histologically. e cumulative incidence was 0.33 %. e median
age of patients with intracranial prostate cancer metastases was 69.8 years
(range: 62 – 74). e average time interval from the diagnosis of prostate
cancer until detection of brain metastases was 5.7 years (range 1 – 15). In
the three surgical cases resection of the brain metastases led to a signif-
icant improvement of neurological symptoms (NIHSS) and outcome at
discharge (mRS). All three operated metastases were adenocarcinomas of
the prostate.
Conclusion: e presented results are in line with those of previous inter-
national multicenter studies. Brain metastases due to prostate cancer are
rare. Nevertheless, in cases of new neurological decits in patients with
prostate cancer, a cerebral dissemination of the primary tumor has to be
considered in the dierential diagnoses. Considering general prognosis
in the setting of an intracranially metastasized prostate cancer further
studies with larger case numbers and more detailed specications of the
primary tumor are recommended.
Disclosure Statement: e authors declare no conict of interest.
404
Molecular analyses of Glioblastoma patient-derived xenograft
(PDX) models identify potential targets in treatment resistant
tumors
Joshua Alcaniz1; Mathias Dahlmann1; Theresia Conrad1;
Andrea Orthmann1; Johannes Haybaeck2,3,4; Stefanie Krassnig2;
Christina Wodlej3; Anna Maria Birkl-Toeglhofer2,4; Tobias Kratzsch5;
Susanne Antje Kuhn6; Andreas Joedicke7; Fichtner Iduna1,8;
Jens Homann1; Wolfgang Walther1,9
1EPO Berlin-Buch GmbH, Berlin, Deutschland
2Diagnostic & Research Center for Molecular BioMedicine, Institute of Pathology,
Medical University of Graz, Graz, Österreich
3Center for Biomarker Research in Medicine, Graz, Österreich
4Institute of Pathology, Neuropathology and Molecular Pathology, Medical
University of Innsbruck, Innsbruck, Österreich
5Department of Neurosurgery, Charité University Hospital, Berlin, Deutschland
6Department of Neurosurgery, Ernst von Bergmann Hospital, Potsdam,
Deutschland
7Department of Neurosurgery, Vivantes Hospital Berlin Neukölln, Berlin,
Deutschland
8Max Delbrueck Center for Molecular Medicine, Berlin, Deutschland
9Experimental and Clinical Research Center , Charité, Universitätsmedizin Berlin,
Translational Oncology, Berlin, Deutschland
Background: Glioblastoma (GBM) is the most common malignant
brain intrinsic tumor in adults, with about 90% of tumors developing de
novo. eir heterogeneity and aggressive, inltrative growth limit suc-
cess of current standard of care and ecacy of various new therapeutic
approaches. To analyze the molecular mechanisms of tumorigenesis and
resistance to therapy, as well as to identify new therapeutic targets, mod-
els reecting the complex biology of these tumors are urgently needed.
erefore patient-derived xenogra (PDX) models are an essential tool
in GBM research.
Methods: We established a panel of 27 PDX glioma models on immu-
nodecient mice (6 of these by othotopic transplantation). Sensitivity
towards a panel of drugs, selected on their modes of action or ability to
pass the blood-brain-barrier (BBB) was determined. Currently, 19 models
have been analyzed for mutations and gene expression proles using panel
and transcriptome sequencing.
Results: Best treatment responses (growth inhibition > 50%) were
observed for SoC Temozolomide (TMZ), Irinotecan and Bevacizumab.
Molecular characterization allowed the identication of frequent muta-
tions - i.e. in the genes KDR, FGFR3, PIK3CA, PTEN and P53 - and
expression signatures, like the activation of upstream regulators HDAC1/2
and ATM in TMZ resistant models. Identied potential new predictive
markers and targets are currently being analyzed.
Discussion: Our sensitivity screens identied irinotecan or bevacizumab
as treatment alternatives in most TMZ resistant PDX models. For their
benecial use in GBM treatment however, there is still need for predictive
markers.
Conclusion: e established PDX panel is a valuable tool to validate
these, as well as to identify new possible targets and assess new treatment
approaches.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 47
460
Tumor Treating Fields reduce the survival and migration
potential of human mesenchymal stromal cells
Alexander Rühle1,2; Maren Strack1,2; Yaara Porat3; Moshe Giladi3;
Anca-L. Grosu1,2; Nils Henrik Nicolay1,2
1Klinik für Strahlenheilkunde, Universitätsklinikum Freiburg, Freiburg im
Breisgau, Deutschland
2Deutsches Konsortium für Translationale Krebsforschung (DKTK),
Partnerstandort Freiburg, Deutsches Krebsforschungszentrum (DKFZ),
Heidelberg, Deutschland
3Novocure Ltd., Haifa, Israel
Background: Tumor Treating Fields (TTFields) have shown clinical e-
cacy in glioblastoma treatment. As mesenchymal stromal cells (MSCs)
belong to the glioblastoma microenvironment and impair the prognosis
of glioblastoma patients, we studied the eects of TTFields on the sur-
vival, migration potential and stem cell characteristics of MSCs.
Methods: Human MSCs were harvested from the bone marrow of three
donors and treated with TTFields for 72h using the inovitro™ system.
Clonogenic survival, proliferation and resazurin assays were conducted
with dierent TTFields frequencies and eld intensities. TTFields-
induced senescence was quantied with β-galactosidase stainings, and
ow cytometry analyses were performed to analyze MSCs’ characteristic
surface marker expression and apoptosis rates. Boyden chamber assays
were carried out to measure the inuence of TTFields on MSCs’ migration
potential.
Result: TTFields reduced cellular proliferation of all analyzed MSC sam-
ples by 45-60% compared to untreated controls, whereas MSCs’ clono-
genic survival was reduced by 73–88%. In contrast, metabolic viability
of MSCs was largely unaected aer TTFields. e anti-proliferative
eect of TTFields on MSCs was relatively independent of the alternat-
ing currents frequency within a range of 100-500 kHz. TTFields resulted
in signicantly increased senescence and apoptosis rates, as detected by
increased caspase-3 and annexin-V levels, while the characteristic MSC-
surface marker expression was found intact. TTFields led to a signicantly
impaired migratory potential of MSCs.
Discussion: MSCs are able to migrate to glioblastoma cells and exert
pleiotropic pro-tumorigenic eects (e.g., neo-angiogenesis, immunosup-
pression, resistance to radiotherapy). e observed sensitivity of MSCs
towards TTFields may therefore contribute to the anti-glioblastoma
eects of TTFields.
Conclusion: Human MSCs exhibit a TTFields-sensitive phenotype, pro-
viding a rationale to target tumor-associated MSCs as part of the glioblas-
toma microenvironment using TTFields.
Disclosure Statement: e authors declare the following:
e project received research funding by Novocure Ltd., and Yaara Porat and
Moshe Giladi are paid full-time employees of Novocure. Alexander Rühle served
as consultant for Novocure Ltd.
465
Bcl6- a potential marker of prognosis in glioblastoma patients
Hannes Treiber1; Christian von der Brelie2; Judith Büntzel1
1Georg-August-Universität, Universitätsmedizin Göttingen, Klinik für
Hämatologie und Onkologie, Göttingen, Deutschland
2Georg-August-Universität, Universitätsmedizin Göttingen, Klinik für
Neurochirurgie, Göttingen, Deutschland
Background: Response to treatment aer surgery and radiation ther-
apy is evaluated by MRI scan in glioblastoma patients. However, MRI
scan does not always dierentiate between early progression and pseu-
do-progression. A discriminating biomarker does not exist. B-cell lym-
phoma 6 (BCL6) plays a central role in lymphocyte maturation and
lymphomagenesis, but was recently found upregulated in glioblastoma
tissue. Wehypothesized that bcl6 may serve as a biomarker accessible via
extracellular vesicles of cancer cells which are secreted into the peripheral
blood.
Methods: Small extracellular vesicles (sEV) were extracted from the
peripheral blood of 37 glioblastoma patients by dierential centrifugation.
Western blotting was used to assess BCL6 content of sEV. BCL6 status of
patients were either rated as “positive” or “negative”. BCL6 status was cor-
related with overall survival using Kaplan-Meier curves.
Result: BCL6 was observed in the sEV of a sub-cohort of 22 glioblastoma
patients. is group showed an overall survival (OS) of 15.6 months,
whereas BCL6-negative patients had an OS of 35.6 months (p = 0.016). All
patients with recurrent disease (N=6) were positive for BCL6 expression
in sEV. All BCL6-negative patients were recruited during stable disease or
at the time of primary diagnosis.
Discussion: We demonstrate presence of BCL6 protein in sEVs. Detection
of BCL6 in sEV was correlated with worse prognosis in glioblastoma
patients and may represent clonal evolution during the disease. Assessing
BCL6 status may have prognostic implications and help to dierentiate
between progression and pseudo-progression. However, a prospective
trial with a larger cohort is required to validate the value of BCL6 as a
biomarker in glioblastoma.
Conclusion: BCL6 has the potential to become a marker for progressive
disease and worse prognosis in glioblastoma patients.
Disclosure Statement: e authors declare no conict of interest.
474
Pseudomyogenic hemangioendothelioma with ACTB-FOSB
gene fusion: case report of intracerebral metastases
Anja Glien1; Lhagva Sanchin1; Dirk Vordermark2; Timo Behlendorf3;
Hans-Jörg Meisel1; Christian Mawrin4
1Klinik für Neurochirurgie, BG Klinikum Bergmannstrost Halle, Halle,
Deutschland
2Universitätsklinik und Poliklinik für Strahlentherapie, Universitätsklinikum Halle,
Halle, Deutschland
3Onkologische Gemeinschaftspraxis, Halle, Deutschland
4Institut für Neuropathologie, Otto-von-Guericke Universität, Magdeburg,
Deutschland
Background: Pseudomyogenic hemangioendothelioma (PMH) is a rare
vascular tumor, oen occuring multifocal, predominantly involving
the trunk or extremities and aecting men of younger age. Described
as a tumor entity of indolent behavior, it was classied in the WHO
Classication of tumors of so tissue and bone in 2013 with low met-
astatic potential. Typically PMH tumors are resected, but two-thirds of
cases show multifocal lesions, oen involving dierent types of tissue
simultaneously. Metastases are almost uncommon, distant metastases
presenting at initial diagnosis seem to be extremely rare. Resection is oen
dicult, moreover a signicant risk of local recurrence is described. To
date, in case of unresectable tumor lesions eective therapeutic strategies
have not been established. In some cases radiotherapy is applied, while
chemotherapy mostly seems to be ineective. However, mTOR inhibitors
showed promising results of disease stabilization.
Methods: Herein, we present a case of a 59-year-old male with multi-
ple intracerebral metastases of a PMH who was treated with stereotactic
radiotherapy, followed by systemic therapy.
Result: Histopathologic examination revealed a pseudomyogenic heman-
gioendothelioma. Molecular analysis identied a ACTB-FOSB gene
fusion, and immunohistochemistry showed expression of somatostatin
receptors in the tumor tissue.
Conclusion: PMH with distant metastases occurring in the central ner-
vous system is extremely rare and needs identication of systemic treat-
ment options.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts48
758
Dexamethasone blunts the ecacy of locally administered
immunostimulatory gene therapy in murine glioblastoma
Marilin Koch1,2; Mykola Zdioruk1; Michael Nowicki1; Alec Grith3;
Estuardo Aguilar-Cordova4; Laura Aguilar4; Francesca Barone4;
Brian W Guzik4; Paul Peter Tak4; Ghazaleh Tabatabai2; James Lederer3;
E. Antonio Chiocca1; Sean Lawler1
1Harvey Cushing Neurooncology Laboratories, Department of Neurosurgery,
Brigham & Womens Hospital, Harvard Medical School, Boston, USA
2Department of Neurology and Interdisciplinary Neuro-Oncology, Hertie
Institute for Clinical Brain Research, Eberhard Karls University Tübingen,
Tübingen, Deutschland
3Department of Surgery, Brigham & Womens Hospital, Harvard Medical School,
Boston, USA
4Candel Therapeutics, Needham, USA
Background: Local immunostimulatory therapies are a promising
approach in the treatment of glioblastoma. e corticosteroid, dexa-
methasone, is frequently required to alleviate edema in this disease
and may compromise the ecacy of immunotherapies. CAN-2409 is a
locally administered immunotherapy that uses aglatimagene besadenovec
(AdV-tk) with an anti-herpetic prodrug to induce tumor cell death by
attracting immune cells to the tumor site. How combined dexamethasone
inuences ecacy of this and other local immunotherapies are unknown
Methods: We investigated the impact of dexamethasone on CAN-2409 in
vitro by cell viability and T-cell mediated tumor killing assays and in vivo
using an orthotopic syngeneic glioblastoma mouse model. Alterations of
the tumor microenvironment in experimental groups were assessed by
mass cytometry (CyTOF) analyses.
Result: In vitro assays showed that dexamethasone signicantly impaired
CAN-2409 mediated anti-tumor cytotoxicity and immunogenicity. In vivo,
we observed a signicant reduction in median survival (29d) of CAN-
2409 and dexamethasone combined treatment as compared to CAN-2409
alone (39.5d) (p= 0.018). CyTOF analyses demonstrated an increase in
macrophage and neutrophil populations and a decrease in T-cells and
B-cells in mice treated with dexamethasone and CAN-2409. Tumor inl-
trating immune cells from mice treated with dexamethasone expressed
higher immune cell exhaustion and pro-tumorigenic cell markers.
Discussion: Our data suggest that dexamethasone may reduce the ecacy
of locally delivered immunotherapies in glioblastoma.
Conclusion: ese results support the idea that dexamethasone use
should be avoided or limited to the lowest necessary dose.
Disclosure Statement: e authors declare no conict of interest.
768
Targeting c-IAP1, c-IAP2, and Bcl-2 eliminates senescent
glioblastoma cells following temozolomide treatment
Christian Schwarzenbach; Larissa Tatsch; Juliana Brandstetter Vilar;
Birgit Rasenberger; Lea Beltzig; Bernd Kaina; Maja Tomicic;
Markus Christmann
Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Institut für
Toxikologie, Mainz, Deutschland
Background: Glioblastoma multiforme is the most aggressive, highly
recurring form of diuse brain tumours and rst-line therapy is composed
of resection followed by ionizing radiation and adjuvant TMZ dosage. In
previous work, we showed that TMZ induces mostly senescence and not
cell death, which is associated with a G2-phase arrest and an increase in
polyploidy. We aimed to identify senolytic drugs to increase the ecacy of
glioblastoma treatment and reduce its burden on the patient.
Methods: erefore, cell death, senescence, cell cycle progression
were analysed by ow cytometry and the expression of senescent cell
anti-apoptotic factors (SCAFs) was analysed by qPCR and immunodetec-
tion in LN229, U87 and A172 glioblastoma cells upon exposure to TMZ.
Furthermore, we evaluated the impact of these potential SCAFs on cell
death by making use of the small molecule inhibitors embelin (targets
XIAP), AT406 (targets c-IAP1 > XIAP), BV6 (targets c-IAP1, c-IAP2
and marginal XIAP) and Venetoclax (targets Bcl-2) and performed
COMBENEFIT analysis for synergy.
Result: SCAFs Bcl-2, Bcl-XL and c-IAP1, c-IAP2 showed strong
expression. Exposure of TMZ-induced senescent cells to non-toxic
concentrations of the inhibitors showed that BV6 and Venetoclax sig-
nicantly induced subG1- and AnnexinV/PI- positive cells, alone and in
combination.
Conclusion: We conclude that the upregulation of the antiapoptotic fac-
tors c-IAP1, c-IAP2 and Bcl-2 during TMZ-induced senescence is a key
event in the protection from cell death, and inhibition of these factors
eectively kills senescent glioblastoma cells.
Indication of source:
1 Schwarzenbach, C.; Tatsch, L.; Brandstetter Vilar, J.; Rasenberger, B.; Beltzig, L.;
Kaina, B.; Tomicic, M.T.; Christmann, M. Targeting c-IAP1, c-IAP2, and Bcl-2
Eliminates Senescent Glioblastoma Cells Following Temozolomide Treatment.
Cancers 2021, 13, 3585.
Disclosure Statement: e authors declare no conict of interest.
847
The Role of Stereotactic Radiosurgery in the Management
of Foramen Magnum Meningiomas — A Multicenter Analysis
Felix Ehret1; Markus Kufeld2; Christoph Fürweger2; Alfred Haidenberger2;
Susanne Fichte3; Ralph Lehrke4; Carolin Senger1; David Kaul1; Martin Bleif5;
Gerd Becker5; Daniel Rueß6; Maximilian Ruge6; Christian Schichor7;
Jörg-Christian Tonn7; Alexander Muacevic2
1Charité - Universitätsmedizin Berlin, Berlin, Deutschland
2Europäisches Radiochirurgie Centrum, München, Deutschland
3CyberKnife Zentrum Mitteldeutschland, Erfurt, Deutschland
4Deutsches CyberKnife Zentrum, Westfalen, Deutschland
5RadioChirurgicum, Göppingen, Deutschland
6Universitätsklinik Köln, Köln, Deutschland
7Ludwig-Maximilians-Universität München, München, Deutschland
Background: Foramen magnum meningiomas (FMMs) represent a
considerable neurosurgical challenge given their location and potential
morbidity. Stereotactic radiosurgery (SRS) is an established non-invasive
treatment modality for various brain tumors. However, reports on SRS
or fractionated stereotactic radiotherapy for the management of FMMs
are rare. Herein, we report our multicenter treatment experience utilizing
robotic radiosurgery.
Methods: Patients who underwent SRS between 2005 and 2020 as a treat-
ment for FMMs at six dierent centers were eligible for analysis. All treat-
ments were delivered using the CyberKnife robotic radiosurgery system
(Accuray Inc., Sunnyvale, CA, USA). Local tumor control (LC), symp-
toms, and adverse events were evaluated clinically and radiographically.
Result: Sixty-two patients were included. e median follow-up was 28.9
months. e median prescription dose and isodose line were 14 Gy and
70%, respectively. Single-fraction SRS accounted for 81% of treatments.
Ten patients were treated for a tumor recurrence aer surgery, and thir-
teen underwent adjuvant treatment. e remaining 39 FMMs received
SRS as their primary treatment. e median tumor volume was 2.6 cubic
centimeters. No local failures were observed, leading to an overall LC of
100%. Tumor volume signicantly decreased aer treatment (p < 0.01).
Most patients showed stable (47%) or improved (21%) neurological de-
cits at the last follow-up. No high-grade adverse events were observed.
Discussion: SRS treatment results for FMMs were favorable and in agree-
ment with the available literature. No signicant toxicity was observed.
Given the potential implications of surgical resection, SRS can be a viable
treatment alternative in patients, especially in those with subtotal tumor
resections, recurrences, and patients not suitable for surgery.
Conclusion: SRS is an eective and safe treatment modality for FMMs.
Despite the paucity of available data, SRS should be considered for
selected patients.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 49
943
First clinical experience on fractionated intracavitary
radioimmunotherapy with Lu-177 labeled 6A10 Fab
fragments in glioblastoma
Michael Müther1; Wolfgang Roll2; Guido Böning3; Astrid Delker4;
Franz-Josef Gildehaus4; Michael Schäfers2; Reinhard Zeidler5;
Hans-Jürgen Reulen6; Lars Stegger2; Walter Stummer1
1Münster, Universitätsklinikum Münster, Klinik für Neurochirurgie, Münster,
Deutschland
2Münster, Universitätsklinikum Münster, Klinik für Nuklearmedizin, Münster,
Deutschland
3Universität München, Klinikum Großhadern, Klinik für Nuklearmedizin,
München, Deutschland
4Universität München, Klinikum Großhadern, Klinik für Nuklearmedizin,
München, Deutschland
5Helmholtz Zentrum München, München, Deutschland
6Universität München, Klinikum Großhadern, Klinik für Neurochirurgie,
München, Deutschland
Background: Maintenance therapies for glioblastoma are lacking.
Adjuvant radio-immunotherapy (RIT) with Lu-177 labeled 6A10-Fab
fragments, targeting tumor-associated carbonic anhydrase XII (CA12),
applied into the resection cavity, oers a promising strategy to address
hibernating tumor burden. We report on the rst in human applications.
Methods: ree patients underwent microsurgical resection of glioblas-
toma. Aer completion of standard adjuvant radio- and chemotherapy,
RIT was oered as compassionate use. Aer implantation of an injection
reservoir into the tumor cavity, the protocol included three consecutive
doses of Lu-177 labeled 6A10 Fab fragments over three months, cor-
responding to 25% - 50% - 25% of the total activity. Injected dose was
adapted to the size of the resection cavity. Dosimetry was performed with
planar whole-body scintigraphy and SPECT/CT 12h, 24h, 48h, 76h and
5-7 days aer injection.
Result: Patient #1 (IDH1-Mutation) received three doses of RIT (592
MBq) with stable disease 12 months aer therapy and 26 months aer ini-
tial diagnosis. Patient (IDH-Wildtype) #2 had histologically proven tumor
progression aer the second cycle (526 MBq). Patient #3 (IDH-Wildtype)
has so far received the one cycle (administered 327 MBq, planned total
1300 MBq). No toxicity according to CTCAE version 6.0 or other adverse
events related to RIT were observed. Dosimetry did not reveal absorbed
doses above the upper dose limit for organs at risk. In the rst two patients,
the calculated absorbed kidney dose was approximately 3.0 +- 1.0 mGy/
MBq and the hematopoietic bone marrow was 0.04 +- 0.01 mGy/MBq.
Discussion: Intracavitary radioimmunotherapy with Lu-177 labeled
6A10-Fab fragments appears to be a safe maintenance therapy for glio-
blastoma patients, albeit only assessed in three compassionate use situ-
ations far.
Conclusion: A multicenter conrmatory phase-I-trial will be initiated in
May 2022 (EudraCT-No: 2015-004417-25) to determine the maximum
tolerated dose and safety of adjuvant RIT with Lu-177 labeled 6A10-Fab
fragments.
Disclosure Statement: e authors declare no conict of interest.
Developmental Therapeutics: Immunotherapy/Cellular
Best-of-Abstract-Vortrag
208
Idecabtagene vicleucel (ide-cel, bb2121) in Relapsed
and Refractory Multiple Myeloma (RRMM): Analyses of
High-Risk Subgroups in the KarMMa Study
Hartmut Goldschmidt1; Noopur Raje2; David Siegel3; Sundar Jagannath4;
Sagar Lonial5; Nikhil Munshi6; Philippe Moreau7; Michele Cavo8;
Anna Truppel-Hartmann9; Everton Rowe10; Liping Huang10;
Amit Agarwal10; Julie Wang10; Timothy Campbell10; Jesus San-Miguel11;
Donna Reece12
1University Hospital Heidelberg and National Center for Tumor Diseases,
Heidelberg, Deutschland
2Massachusetts General Hospital, Boston, USA
3Hackensack University Medical Center, Hackensack, USA
4Mount Sinai Hospital, New York, USA
5Emory School of Medicine, Atlanta, USA
6Jerome Lipper Multiple Myeloma Center and LeBow Institute for Myeloma
Therapeutic, Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA
7Centre Hospitalier Universitaire de Nantes, Nantes, Frankreich
8Seràgnoli Institute of Hematology, Bologna University School of Medicine,
Bologna, Italien
9bluebird bio, Cambridge, USA
10Bristol Myers Squibb, Princeton, USA
11Clinica Universidad de Navarra, CIMA, IDISNA, CIBERONC, Navarra, Spanien
12Princess Margaret Cancer Centre, Toronto, Kanada
Background:Patients (pts) with high-risk RRMM receiving conventional
care face poor outcomes. Ide-cel, a BCMA-directed CAR T cell therapy
(tx), demonstrated frequent, deep and durable responses in RRMM pts in
the pivotal phase 2 KarMMa study (NCT03361748).1 We report updated
safety and ecacy results for ide-cel in high-risk subgroups from the
KarMMa study.
Methods:Pts had ≥3 prior lines of tx (immunomodulatory agent, prote-
asome inhibitor, and anti-CD38 antibody inclusive) and were refractory
to their last regimen. Aer lymphodepletion, pts received target doses
of 150–450 × 106 CAR+ T cells.1 Subgroup analyses were performed in
pts stratied by extramedullary disease (EMD), high-risk cytogenet-
ics [del(17p), t(4;14), t(14;16)], high tumor burden (≥50% bone mar-
row plasma cells), receipt of bridging tx, baseline disease stage (revised
International Staging System), and >1 prior regimen/year. Primary end-
point was overall response rate (ORR).
Results:Among 128 ide-cel–treated pts, 39% had EMD, 35% had high-
risk cytogenetics, 51% had high tumor burden, 88% received bridging tx,
16% had disease stage III, and 47% received >1 prior regimen/year. At the
cuto date (21 Dec 2020), ORR was ≥65% and complete response rate
was ≥22% across all high-risk subgroups examined except disease stage
III (48% and 10%, respectively). ORR was not substantially aected by
presence of EMD (70% w/ and 76% w/o) or high baseline tumor burden
(71% w/ and 77% w/o). Median duration of response was ≥9.2 mo and
median progression-free survival was ≥6.1 mo in all high-risk subgroups
except disease stage III (6.9 mo and 4.9 mo, respectively). No new safety
signals were identied.
Discussion: Ide-cel continues to demonstrate benet, even in historically
dicult-to-treat pts, including pts with high-risk features such as EMD,
high-risk cytogenetics, high tumor burden, and receipt of bridging tx or
>1 prior regimen/year.
Conclusions: ese results suggest that ide-cel represents a promising
treatment option for pts with high-risk RRMM.
Reference:
1. Munshi NC, et al.N Engl J Med 2021;384:705–716.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts50
Poster
85
Feasibility of eftilagimod alpha combined with avelumab
in advanced solid tumors: advanced safety and ecacy data
from Stratum D of the phase I INSIGHT platform trial
Thorsten O. Goetze1,2; Daniel W. Mueller1,2; Mohammad-Reza Rayan3;
Dragan Kiselicki3; Timursah Habibzade3; Marina Schaaf2;
DisornSookthai2; Regina Eickho2; Elke Jäger3; Salah-Eddin Al-Batran1,2
1Krankenhaus Nordwest, University Cancer Center Frankfurt, Frankfurt am
Main, Deutschland
2Institut für Klinische Krebsforschung IKF GmbH am Krankenhaus Nordwest,
Frankfurt am Main, Deutschland
3Krankenhaus Nordwest, Frankfurt, Frankfurt am Main, Deutschland
Background: Stratum D of the INSIGHT platform trial evaluates eilagi-
mod alpha (ei) combined with avelumab in advanced solid tumors. Ei
is an MHC class II agonist which activates antigen-presenting cells fol-
lowed by CD8 T-cell activation. Combination with PD-1/PD-L1 blockade
aims at enhanced ecacy.
Methods: is phase I trial consists of 5 strata: intratumoral (A) or intra-
peritoneal ei (B); s.c. ei with SOC (C) or with PD-L1 inhibition (D).
Strat E is currently under development with a new ei combination. is
abstract focuses on Strat D: 800mg avelumab i.v. q2w along with s.c. ei:
6mg (cohort 1, 6 pts), 30mg (cohort 2, 6 pts). e primary endpoint is
safety.
Result: e trial was completed with 12 pts (cohort [coh] 1: gastric, gall-
bladder, colon, pleural mesothelioma; coh 2: gastric, gastroesophageal,
anal, rectum, cervix uteri). No dose limiting toxicities occurred. 10 serious
adverse events were reported, none of them related to the IMPs (4 SAEs
in 3 pts coh 1 [1 acute renal insuciency grade 5 in 1 pt, 2 preileus grade
3 in 1 pt, 1 hearing impaired grade 4 in 1 pt] and 6 SAEs in 4 pts coh 2
[1 anal hemorrhage and 1 gallbladder obstruction in 1 pt, 1 eye pain and
1 feeding tube dislocation in 1 pt, each grade 3, 1 skin infection grade
2, 1 diuse myocardial brosis grade 5]. 1 AE of special interest (AESI)
related to avelumab (sarcoidosis grade 1) occurred. 2 pts completed max
treatment with 24 cycles. 5 pts showed partial response, 1 stable disease,
5 progressive disease acc. to RECIST 1.1, 1 clinical progression. Activity
was also observed in pre-treated non- immunogenic tumors. In the entire
study population 75% were still alive, 66.7% of coh 1, 83.3% of coh 2.
Discussion: Treatment with avelumab and ei 6mg or 30mg was well tol-
erated with no unexpected AEs. Signals of ecacy targeting the axis of
PD-L1 in combination LAG-3-agonism were seen (disease control rate
of 50%).
Conclusion: 30 mg ei appears to be feasible and safe.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
86
Co-stimulatory bispecic antibodies induce enhanced T cell
activation and tumor cell killing in breast cancer models
Karsten Michael Warwas1,2; Marten Meyer1,2; Márcia Gonçalves1,2;
Annkathrin Teschner1,2; Gerhard Moldenhauer3; Claus Peter Heußel4,5,6;
Inka Zörnig7; Dirk Jäger1,7; Frank Momburg2,7
1German Cancer Research Center (DKFZ), Clinical Cooperation Unit Applied
Tumor Immunity, Heidelberg, Deutschland
2German Cancer Research Center (DKFZ), Antigen Presentation and T/NK Cell
Activation Group, Heidelberg, Deutschland
3German Cancer Research Center (DKFZ), Department of Translational
Immunology, Heidelberg, Deutschland
4University Hospital Heidelberg, Thoraxklinik Heidelberg, Diagnostic and
Interventional Radiology with Nuclear Medicine, Heidelberg, Deutschland
5University Hospital Heidelberg, Department of Diagnostic and Interventional
Radiology, Heidelberg, Deutschland
6German Lung Research Center (DZL), Translational Lung Research Center
Heidelberg (TLRC), Heidelberg, Deutschland
7University Hospital Heidelberg, National Center for Tumor Diseases (NCT),
Department of Medical Oncology, Heidelberg, Deutschland
Background: Although T cell-recruiting CD3-binding bispecic anti-
bodies (BiMAb) are clinically eective for hematologic malignancies, the
success of BiMAb targeting solid tumor-associated antigens (TAA) in
carcinomas remains poor. We reasoned that provision of co-stimulatory
BiMAb in combination with αCD3 BiMAb would boost T cell responses,
facilitating targeting of weakly or heterogeneously expressed tumor
antigens.
Methods: We analyzed αTAA–αCD3/αCD28 BiMAb, targeting breast
cancer antigens including HER2, EGFR, CEA, and EpCAM. Moreover,
we tested bifunctional fusion proteins of tumor necrosis factor ligand
(TNFL) superfamily members such as 4-1BBL, OX40L, CD70 and TL1A.
Functional activity was evaluated in cell-based assays. Anti-tumor activity
was conrmed in a patient-derived 3D spheroid model using pleural eu-
sions of breast cancer patients.
Result: Only in presence of tumor cells, αCD3 BiMAb activated T
cells and induced cytotoxicity in vitro, indicating strict dependence on
cross-linking. Combination treatment of αCD3 with αCD28 or TNFL
bispecics drastically enhanced T cell proliferation, activation marker
expression, cytokine secretion and tumor cytotoxicity, reducing the
required dose to achieve T cell activation. Immune checkpoint inhibi-
tors further augmented BiMAb-mediated co-stimulation. In patient-de-
rived spheroids, co-stimulatory BiMAb were essential for activation
of tumor-inltrating lymphocytes and cytotoxic anti-tumor responses
against breast cancercells.
Discussion: Co-stimulatory bispecics signicantly potentiated the
tumoricidal activity of αCD3 BiMAb while preserving dependence on
TAA recognition. When co-stimulation involves a second tumor-associ-
ated antigen or a tumor stromal antigen, such approach could provide for
a more localized activation of the immune system with higher ecacy and
reduced peripheral toxicities.
Conclusion: Combining stimulatory and co-stimulatory BiMAb may
have promising clinical application in the treatment of solid tumors.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 51
89
Recurrence of hepatocellular carcinoma can be predicted by
PD-1 expression and immune-active lymphocytes
Gabriel Fridolin Hess1,2; Jasmin Zeindler1; Silvio Däster1; Simone Muenst3;
Caner Ercan2,3; Jürg Vosbeck3; Mairene Coto-Llerena2,3;
Salvatore Piscuoglio2,3; Otto Kollmar1; Savas Deniz Soysal1
1Clarunis Viszeralchirurgie, Universitätsspital Basel , Basel, Schweiz
2Departement Biomedizin, Universität Basel und Universitätsspital Basel, Basel,
Schweiz
3Pathologie, Universitätsspital Basel , Basel, Schweiz
Purpose: Manipulation of the immune system by tumors leads to com-
promised antigen recognition and an immunosuppressive microenviron-
ment. One immunomodulatory strategy employed by malignant tumors
is expression of the programmed cell death receptor 1 ligand (PD-L1), the
receptor for which is expressed on activated T cells (PD-1). Expression of
PD1 and PD-L1 in the tumor has prognostic importance in a variety of
malignancies and can predict response to so-called immune checkpoint
inhibitors directed against PD-1 or PD-L1.
Hepatocellular carcinoma (HCC) is the most common primary liver
malignancy, and targeted therapies against this tumor are rare.
e aim of our study was to investigate the impact of PD-1 and PD-L1
expression on HCC recurrence.
Methods: Immunohistochemical staining against PD-1 (NAT105) and
PD-L1 (Ventana SP263) was performed on tissue from 91 postopera-
tive HCC patients. Tumors were classied as immunologically active,
excluded or deserted. PD-1 and PD-L1 immunoreactivity was evaluated
as the proportion of positive staining of the total number of immune cells
(0%, <1% and >1%).
Results: HCC recurrence was signicantly associated with the
immune-excluded subclass. e majority of non-recurrent HCC showed
PD-1 expression >1% (80%; 37/46). Conversely, recurrent HCC showed
PD-1 expression 0% or <1% in 45% (20/45) of the cases. Of note, HCC
classied as immune active were enriched for PD-1 >1% positive cells
(74%; 46/62). No association was found between PD-L1 expression on
tumor cells and HCC recurrence.
Discussion: In concordance with previous reports we found an asso-
ciation between low frequency of PD-1 expression and increased HCC
recurrence. Our results regarding the lack of impact of PD-L1 expression
on HCC recurrence are in line with previous studies in the literature. In
addition, our results suggest that HCC recurrence may be more frequent
in immune-exclusive tumors.
Conclusions: Our results show a higher rate of recurrence in patients
with fewer PD-1 positive tumor inltrating lymphocytes. e expression
of PD-L1 does not seem to be a prognostic marker in HCC.
Disclosure Statement: e authors declare no conict of interest.
296
Clinical scale production of BCMA CAR T cells comprising a
dened early memory phenotype
Jara J. Joedicke1; Ulrich Großkinsky1; Uta E. Höpken2; Armin Rehm1
1Max-Delbrück-Center for Molecular Medicine, Department of Translational
Tumorimmunology, Berlin, Deutschland
2Max-Delbrück-Center for Molecular Medicine, Department of
Microenvironmental Regulation in Autoimmunity and Cancer, Berlin,
Deutschland
Background: Clinical studies on CAR T cells targeting B cell neoplasm
have shown remarkable success rates. However, frequent relapses and
primary refractoriness remain challenging. Dening CAR T cell starting
populations, can prevent production failure, yield a more homogenous
CAR T cell product, and thereby prevent early remission aer CAR T cell
therapy.
Methods: To produce early memory BCMA CAR T cells we combined the
fully-closed bioreactor system CliniMACS Prodigy with an S2 cell sorter.
Apheresis material was introduced into the Prodigy, depleted of RBCs and
MACS puried for CD4+/CD8+ cells. e cells were retrieved from the
system, antibody-stained for CD62L/CD95 and FACS sorted for double
positive cells under aseptic conditions. e puried early memory T cells
were reapplied to the Prodigy system. Subsequently, T cells were activated,
γ-retrovirally transduced with a BCMA-CAR encoding SIN vector and
expanded in a memory enhancing cytokine milieu.
Result: Sorting and subsequent culture in IL7/IL15 containing medium
resulted in an increased early memory phenotype in both CD4+ and CD8+
CAR T cells, when compared to bulk runs. Despite lower starting cell
numbers of highly enriched early memory T cells, the process resulted in
clinically relevant CAR T cell yields with maintained eector functions.
Discussion: With our newly established protocol, combining the Prodigy
with an aseptic sorting step, we showed the successful production of func-
tional BCMA CAR T cells with an early memory phenotype from a lim-
ited number of starting T cells.
Conclusion: We developed an economic and safe production protocol for
dened CAR T cell populations at a clinical scale.
Disclosure Statement: e authors declare no conict of interest.
307
Extracorporal photopheresis for immune-related adverse
events after checkpoint inhibitor treatment – a multicenter
survey
Petya Apostolova1; Jan-Malte Placke2; Susanne Unger3; Sophie Giesler1;
James Hutchinson4; Sebastian Haferkamp5; Theresa Lowinus1;
Justus Duyster1; Carolin Funke-Lorenz2; David Rafei-Shamsabadi6;
Frank Meiss6; Burkhard Becher3; Robert Zeiser1
1Medical Center, Albert-Ludwigs University, Freiburg, Germany, Department of
Medicine I, Faculty of Medicine, Freiburg, Deutschland
2University of Essen, Department of Dermatology, Essen, Deutschland
3Institute of Experimental Immunology, University of Zurich, Zürich, Schweiz
4University Hospital Regensburg, Regensburg, Department of Surgery,
Regensburg, Deutschland
5University Hospital Regensburg, Regensburg, Department of Dermatology,
Regensburg, Deutschland
6Medical CenterUniversity of Freiburg, Department of Dermatology, Freiburg,
Deutschland
Treatment with immune checkpoint inhibitors (ICI) has improved the
long-term prognosis of many patients with metastatic tumors. However,
immune-related adverse events (irAE) occur in up to 50% of all ICI-
treated individuals. Treatment of irAE consists of glucocorticosteroids,
other immunosuppressive agents and interruption of ICI-based immu-
notherapy. ese approaches are based on clinical experience rather than
on prospective phase-III trial data. 20-50% of the irAE patients do not
achieve a complete remission upon glucocorticosteroid therapy, or expe-
rience irAE relapse when immunosuppressive medication is tapered. We
have previously described the successful treatment of checkpoint inhibi-
tor-induced colitis with extracorporeal photopheresis (ECP) (Apostolova
NEJM 2020). Here, we present a retrospective survey on the use of ECP
for the treatment of irAE. Seven patients were treated at three dierent
cancer centers between April 2018 and August 2021, for ICI-related colitis
(7/7 patients, 100%) and arthralgia (1/7 patients, 14.3%). e underly-
ing malignancies included melanoma (6/7 patients, 85.7%) and renal cell
cancer (1/7 patients, 14.3%). e median duration of ECP treatment was
22 weeks, and the median number of ECP-procedures was 16. Complete
resolution of irAEs occurred in six of seven patients (85.7%) and one
patient was stabilised following ECP. e median time to response was 14
days. ree patients discontinued immunosuppression completely while
on ECP, whereas immunosuppressive therapy was reduced by 43% - 88%
in the other four patients. No serious adverse events were associated with
ECP. Tumor progression occurred in one patient, the other six patients
had an ongoing tumor control (CR n=3; PR n=2, SD n=1) during ECP
treatment.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts52
Our results indicate that ECP for irAE is safe and has clinical activity in
a real-world setting. Deep proling of immune cell population pheno-
type and metabolism is planned in order to decipher how ECP controls
immune pathology leading to the clinical resolution of irAE.
Disclosure Statement: e authors declare the following:
R.Z.: Honorar für Vorträge von Novartis, Incyte und MNK
329
Anti-EMMPRIN antibody h161-pAb disrupts
epithelial-mesenchymal transition in breast and oral
cancercells: a targeted approach to inhibit metastasis
Phillipp Brockmeyer1; Felix Oyelami2,3; Elina Simanovich2;
HenningSchliephake1; Michal A. Rahat2,3
1Department of Oral and Maxillofacial Surgery, University Medical Center
Göttingen, Göttingen, Deutschland
2The Immunotherapy Laboratory, Carmel Medical Center, Haifa, Israel
3The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel
Background: Metastasis is the main reason for cancer-related deaths.
Epithelial-mesenchymal transition (EMT) enhances tumor cell motility
and invasiveness which is critical for metastasis. Tumor associated mac-
rophages (TAMs) secret EMT inducing cytokines. Molecules mediating
TAM-tumor cell interactions and promoting EMT are not well known.
Transmembranal protein EMMPRIN has been implicated in EMT and
could be a target for an antimetastatic therapy approach.
Methods: Human monocytic cell line U937 was co-cultured with human
breast carcinoma cells (MCF7 or MDA-MB-231) or oral carcinoma cells
(SCC40 and PCI-13), with or without the addition of the newly developed
anti-EMMPRIN antibody h161-pAb. EMMPRIN expression and secre-
tion (IF, WB, ELISA), E-cadherin and vimentin expression (WB, IF), and
cell migration and proliferation (scratch assay, CCK-8) were monitored.
Result: Co-culturing reduced E-cadherin expression in the epithelial-like
MCF7 and SCC40 cells and enhanced their migration relative to the sin-
gle cultures. In contrast, mesenchymal-like cells (MDA-MB-231 or PCI-
13) did not change vimentin expression or their migration. Secretion of
EMT inducers (primarily TGFβ, also TNFα, IGF-1 and EGF, the latter
only in breast cells) was enhanced in all co-cultures. Although EMMPRIN
expression and secretion were unchanged, its activities, including prolifer-
ation and induction of VEGF and MMP-9 secretion, were increased in all
co-cultures, whereas migration was increased only in the epithelial cells.
When h161-pAb was added to the co-cultures, proliferation, migration,
the levels of EMT-inducers and the secretion of VEGF and MMP-9 were
reduced, and vimentin expression was decreased in the mesenchymal-like
cells.
Discussion: Monocytes and EMMPRIN might be important during
metastasis. EMT properties partially overlap with EMMPRIN activity.
H161-pAb reduced the mesenchymal properties of the tumor cellss.
Conclusion: Blocking EMMPRIN activity with h161-pAb may be useful
to decrease metastasis.
Disclosure Statement: e authors declare no conict of interest.
560
Ecacy and Safety of Idecabtagene vicleucel (ide-cel, bb2121)
in Elderly Patients (Pts) with Relapsed and Refractory Multiple
Myeloma (RRMM): KarMMa Subgroup Analysis
Hermann Einsele1; Jesús Berdeja2; Noopur Raje3; David Siegel4; Yi Lin5;
Larry Anderson; Jr6; Paula Rodriguez-Otero7; Salomon Manier8;
Michele Cavo9; Anna Truppel-Hartmann10; Everton Rowe11; Jill Sanford11;
Julie Wang11; Timothy Campbell11; Sundar Jagannath12
1University Hospital of Würzburg, Würzburg, Deutschland
2Sarah Cannon Research Institute and Tennessee Oncology, Nashville, USA
3Massachusetts General Hospital, Boston, USA
4Hackensack University Medical Center, Hackensack, USA
5Mayo Clinic, Rochester, USA
6UT Southwestern Medical Center, Simmons Comprehensive Cancer Center,
Dallas, USA
7Clínical Universidad de Navarra, Pamplona, Spanien
8Service des Maladies du Sang, CHU Lille, Lille, Frankreich
9Seràgnoli Institute of Hematology, Bologna University School of Medicine,
Bologna, Italien
10bluebird bio, Cambridge, USA
11Bristol Myers Squibb, Princeton, USA
12Mount Sinai Medical Center, New York, USA
Background: Advanced age negatively aects prognosis and limits treat-
ment options in pts with multiple myeloma. Idecabtagene vicleucel (ide-
cel, bb2121), a BCMA-directed CAR T cell therapy, showed frequent,
deep and durable responses in the pivotal phase 2 KarMMa study of pts
with triple-class exposed RRMM.1 Here we report updated ecacy and
safety data for ide-cel in elderly pts enrolled in the KarMMa study.
Methods:Pts in the KarMMa trial (NCT03361748) had ≥3 prior lines of
therapy, including an immunomodulatory agent, a proteasome inhibi-
tor, and an anti-CD38 monoclonal antibody, and were refractory to their
last regimen per International Myeloma Working Group (IMWG) crite-
ria. Pts received ide-cel at 150–450 × 106CAR+ T cells aer 3 d of lym-
phodepletion followed by 2 d of rest. e primary endpoint was overall
response rate (ORR). Pts were classied into ≥65 y and ≥70 y subgroups
for analysis. Responses were assessed using IMWG guidelines; duration of
response (DOR) and progression-free survival (PFS) were analyzed with
Kaplan-Meier methods.
Results:Of 128 ide-cel–treated pts, 45 (35%) were ≥65 y and 20 (16%)
were ≥70 y of age. Median age in these age groups was 69 y (range, 65–78)
and 73 y (range, 70–78), and median number of prior antimyeloma reg-
imens was 6 and 5, respectively. At data cuto (21 Dec 2020), response
rates and DOR for both age groups were similar to the overall ide-cel–
treated population; ORR was 84% and 90%, complete response rate was
31% and 35%, and median DOR among responders was 10.9 mo and 11.0
mo in pts aged ≥65 y and ≥70 y, respectively. Median PFS was 8.6 mo (95%
CI, 4.9–12.3) in pts aged ≥65 y and 10.2 mo (95% CI, 3.1–12.4) in pts aged
≥70 y. No new safety signals were identied.
Discussion: ese data suggest that older age (≥70 y) does not signi-
cantly impact PFS following ide-cel treatment.
Conclusions:Ide-cel continues to demonstrate benet with a manageable
safety prole in triple-class exposed pts with RRMM aged ≥65 y and ≥70y.
Outcomes were comparable with the overall ide-cel–treated population.
Reference:
1. Munshi NC, et al.N Engl J Med 2021;384:705–716.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 53
613
The role of TSPO in T cell immune control of glioblastoma
Ayse N. Menevse1; Laura-Marie Ammer2; Arabel Vollmann-Zwerenz2;
Celine Rohrmus2; Marcell Kupczyk1; Markus J. Riemenschneider3;
Nathalie L. Albert4; Peter Bartenstein4; Jörg-Christian Tonn5;
Philipp Beckhove1; Peter Hau2
1RCI Regensburger Centrum für Interventionelle Immunologie, Regensburg,
Deutschland
2Wilhelm Sander NeuroOnkologie , Neurologie, Universitätsklinikum
Regensburg, Regensburg, Deutschland
3Neuropathologie , Universitätsklinikum Regensburg, Regensburg, Deutschland
4Klinik und Poliklinik für Nuklearmedizin , Ludwig-Maximilians-Universität
München, München, Deutschland
5Klinik und Poliklinik für Neurochirugie , Ludwig-Maximilians-Universität
München, München, Deutschland
Background: Glioblastoma (GB) is the most fatal primary brain cancer
in adults. Its malignancy is greatly enhanced by resistance to common
anti-cancer treatments including immunotherapy. Translocator protein
(TSPO) is overexpressed in GB and has been implicated with a functional
role on GB hallmark features including resistance to apoptosis and evad-
ing recognition by the immune system. However, the exact role of TSPO
in GB is unknown. We hypothesize that TSPO contributes to the resis-
tance of GB tumor cells against T cell-mediated killing.
Methods: We established co-cultures of primary brain tumor initiating
cells (BTICs) and allogeneic or autologous T cells. We generated stable
TSPO-knockdown BTICs and measured cytotoxicity and active caspase
3/7 in these co-cultures. In parallel, TSPO-decient BTICs were treated
with apoptosis-inducing cytokines and the eect on the apoptotic cascade
and TSPO expression was evaluated. In addition, we performed RNA
sequencing of TSPO decient versus control BTICs.
Result: TSPO expression was upregulated in BTICs upon contact with T
cells. TNFα and IFNγ were identied as key activators of TSPO expres-
sion. Knockdown of TSPO in BTICs resulted in improved T cell-medi-
ated killing in autologous and allogeneic co-culture settings. BTICs were
resistant to apoptosis inducers TNFα and FasL, whereas TRAIL eectively
activated the apoptotic cascade. More importantly, we showed that down-
regulation of TSPO in BTICs further sensitized cells to TRAIL-induced
apoptosis by activating both intrinsic and extrinsic apoptosis pathways.
Our transcriptome analysis on TSPO decient BTICs revealed downregu-
lated genes that were associated with apoptosis-resistance.
Discussion: Upregulation of TSPO by T cell-derived cytokines might
inuence the therapeutic eect of GB immunotherapy.
Conclusion: Our data provide rst evidence that TSPO is upregulated
upon contact with tumor-reactive T cells. ereby, TSPO may act as resis-
tance mechanism against T cell-mediated apoptosis in GB.
Disclosure Statement: e authors declare no conict of interest.
649
Endogenous T-cell responses to tumor associated antigens are
frequent in esophago-gastric adenocarcinoma and antigen
specic T cells can be expanded using CD40-activated B cells
Martin Thelen1; María García-Márquez1; Jonas Lehmann1;
Diandra Keller1; Ella Preugszat1; Christiane Bruns2; Alexander Quaas3;
Michael von Bergwelt-Baildon4,5,6; Hans Schlößer1,2
1Center for Molecular Medicine Cologne, University of Cologne, Faculty
of Medicine and University Hospital Cologne, Cologne, Germany, Köln,
Deutschland
2Klinik für Allgemein-, Viszeral-, Tumor- und Transplantationschirurgie,
University of Cologne, Faculty of Medicine and University Hospital Cologne,
Cologne, Germany, Klön, Deutschland
3Institute of Pathology, University of Cologne, Faculty of Medicine and University
Hospital Cologne, Cologne, Germany, Köln, Deutschland
4Medizinische Klinik und Poliklinik 3, Ludwig Maximilian Universität München,
München, Deutschland
5Gene Center Munich, Ludwig Maximilians University, Munich, Germany
6German Cancer Consortium (DKTK), Heidelberg, Deutschland
Background: Tumor-associated antigens (TAAs) are major targets of
immunotherapy. erapeutic targeting of TAAs is scalable as they are
shared between patients. Modern cellular therapies, especially those using
combined targeting of multiple antigens have renewed the interest in
TAAs. Our study elucidates the role of TAAs in esophago-gastric adeno-
carcinoma (EGA).
Material and Methods: Nanostring was used to assess expression of 26
TAAs and 25 genes associated with antigen-presentation in tumor sam-
ples and matched normal tissue of 41 treatment-naive EGA patients.
Peptide pools from the 10 most important TAAs were selected and co-cul-
tured with peripheral blood mononuclear cells (PBMCs, n=21) to deter-
mine cellular anti-tumor immune responses in IFN-γ/IL-2 FluoroSpot
assays. e Immune Score was determined using digital image analyses of
immunohistochemical tumor stains (CD3, CD8). Finally, TAA-specic T
cells were expanded using CD40 activated B cells and used to demonstrate
specic killing of tumor cells in-vitro.
Results: CEP55 and MAGEA3/6 showed the highest expression, whereas
expression of NY-ESO-1 was low. 68.3% (28/41) of tumors expressed ≥
5/10 analyzed TAAs simultaneously. Samples with high immune scores
expressed more TAAs and showed higher expression of genes related to
antigen-presentation. TAA-specic immune responses against at least one
TAA were detectable in 75.0% of patients. 6/20 patients showed cellular
responses against ≥5 TAAs simultaneously. We demonstrate feasibility of
TAA-specic T-cell expansion using CD40 activated B cells as a strategy to
induce or enhance TAA-specic immune responses with cytotoxic activ-
ity in EGA. Importantly, endogenous TAA-specic T cell responses were
related to absent expression of the respective TAA in 88.2% of patients.
Conclusion: TAAs are important targets for immuotherapy and immune
monitoring of EGA. Personalized immunotherapeutic strategies target-
ing EGA-specic combinations of TAAs appear highly promising in this
challenging disease. However, additional targeting of immune escape may
be needed.
Disclosure Statement: e authors declare the following:
Advisory Board for BMS; Funding for Research by Astra Zeneca.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts54
681
TCR gene therapy of CD22-positive B cell malignancies
Simone Rhein1; Neşe Çakmak-Görür2; Corinna Grunert2; Elisa Kieback3;
Matthias Leisegang2; Sebastian Ochsenreither2; Antje Siegert4;
Bernadette Brzezicha4; Gerald Willimsky2,5; Ulrich Keller1,2,5;
Thomas Blankenstein1,2; Antonio Pezzutto2; Antonia Busse2
1Max Delbrück Center for Molecular Medicine in Helmholtz Association, Berlin,
Deutschland
2Charité-Universitätsmedizin Berlin, corporate member of Freie Universität
Berlin and Humboldt-Universität zu Berlin, Berlin, Deutschland
3T-knife GmbH, Berlin, Deutschland
4EPO Experimental Pharmacology & Oncology Berlin-Buch GmbH, Berlin,
Deutschland
5German Cancer Consortium (DKTK), Heidelberg, Germany, Partner Site Berlin,
Berlin, Deutschland
Background: CD22 is a suitable alternative to CD19- and CD20-directed
therapies, as these oen lead to downregulation or loss of antigen. CD22-
targeted chimeric antigen receptor (CAR) T cells induce remission in B
cell acute lymphoblastic leukemia (B-ALL), but its ecacy is oen ham-
pered by downmodulation of surface CD22. Since intracellular CD22
expression is maintained in these cases, malignant cells might still be targ-
etable by a CD22-directed T cell receptor (TCR) cell therapy.
Methods: We used a humanized mouse model that is transgenic for the
human TCR α and β gene loci and the human HLA-A*02:01 to generate
TCR specic for a CD22 epitope. Aer molecular cloning of TCRs, TCR-
transduced T cells were tested for ecacy and specicity in vitro and were
tested in a xenogra mouse model.
Result: Lymphoblastoid cell lines (LCLs) expressing high amounts of sur-
face CD22 are equally recognized by CD22 TCR and CAR, while cells
expressing intracellular CD22 are only recognized by CD22 TCR T cells.
Patient and PDX tumor cells were eciently recognized by the CD22 TCR
T cells. e safety analysis of the lead TCR did not reveal any o-target
eects or alloreactivity: a panel of HLA-A2-negative LCLs and around
100 self-peptides eluted from the human peptidome were not recognized
by CD22 TCR T cells. Using Alanine scan the peptide binding motif was
determined, but no other homologous epitopes could be found in the
human proteome. In a xenogra mouse model with Nalm6 cells there was
a slight ecacy advantage of CD22 TCR over CD22 CAR observed.
Discussion: To further prove the advantage of CD22 TCR over CD22
CAR T cells more primary patient samples have to be tested, preferably
from relapsed patients aer a CD19-CAR T cell therapy or aer treatment
with the CD22-targeting agent inotuzumab ozagamicin.
Conclusion: We have demonstrated the ecacy and safety of our lead
CD22 TCR candidate. As this TCR therapy might have the potential to
eectively treat patients relapsed aer CAR T cell therapy, we pursue the
pre-clinical development.
Disclosure Statement: e author Simone Rhein declares the previous
employment by T-Knife GmbH and is currently employed by Epo GmbH.
e project is funded by a cooperation project between MDC and T-knife GmbH.
All other authors declare no conict of interest.
700
ZENYTH-ESO: Master protocol to assess the safety
and recommended phase II dose of next generation
NY-ESO-1-specic TCR T-cells in HLA-A*02 patients with
synovial sarcoma, myxoid/round cell liposarcoma and non-
small cell lung cancer [Substudy 1 (GSK3901961)
and Substudy 2 (GSK3845097)]
Roland Ullrich1; Martin Wermke2; Jerey Yachnin3; Stephan Mielke4;
Reema Patel5; Melinda L Yushak6; Adam J. Schoenfeld7; Jayesh Desai8;
Mehmet Altan9; Sandra P. D’angelo7; Jonathan Noujaim10; John B.A.G.
Haanen11; Benjamin Powers12; Thomas Faitg13; Wenlei Liu13; Nitin Patel13;
Dejka M. Araujo9
1University Clinic Cologne, Köln, Deutschland
2Universitätsklinikum Carl Gustav Carus Dresden, Dresden, Deutschland
3Karolinska Institutet, Solna, Schweden
4Karolinska University Hospital and Institutet, Stockholm, Schweden
5Markey Cancer Center, Lexington, USA
6Emory Winship Cancer Institute, Atlanta, USA
7Memorial Sloan Kettering Cancer Center, New York, USA
8Peter MacCallum Cancer Centre, Melbourne, Australien
9MD Anderson Cancer Center, Texas, USA
10Institut DHématologie-Oncologie, Hôpital Maisonneuve-Rosemont, Montreal,
Kanada
11Antoni van Leeuwenhoek Ziekenhuis, Amsterdam, Niederlande
12University of Kansas Medical Center, Division of Hematology/Oncology,
Department of Internal Medicine, Kansas City, USA
13GlaxoSmithKline, London, Vereinigtes Königreich
Background: Letetresgene autoleucel (lete-cel; GSK3377794) is an
autologous T-cell therapy expressing an anity-enhanced T-cell recep-
tor (TCR) to improve recognition of cancer cells expressing NY-ESO-1
and/or LAGE-1a. GSK3901961 and GSK3845097 are next generation
NY-ESO-1 TCR T-cell therapies. GSK3901961 co-expresses the α-chain
of the CD8 co-receptor to improve T-cell persistence and helper func-
tions. GSK3845097 reduces TGF-β pathway activation and maintains
Tcell proliferation, cytokine production, and cytotoxicity in the tumor
microenvironment.
A rst-time-in-human master protocol (NCT04526509) will evaluate
the safety, tolerability, and recommended Phase 2 dose (RP2D) of NY-ESO-
1-specic TCR T-cell therapies. Substudy 1 will assess GSK3901961 in
advanced non-small cell lung cancer (NSCLC), or advanced synovial sar-
coma (SS) or myxoid/round cell liposarcoma (MRCLS). Substudy 2 will
assess GSK3845097 in advanced SS or MRCLS.
Methods: Each substudy includes a dose conrmation stage to assess RP2D
and a dose expansion stage, aiming to dose 10 participants at the RP2D.
Key inclusion criteria: age ≥18 years; measurable disease per RECIST
v1.1; HLA-A*02:01, A*02:05, or A*02:06 positivity; NY-ESO-1/LAGE-1a
tumor expression; Substudy 1: Stage IV NSCLC, receipt of ≥1 prior line(s)
of standard of care therapy; Substudy 1, and Substudy 2: advanced (met-
astatic/unresectable) SS or MRCLS; and prior anthracycline-based ther-
apy. Key exclusion criteria: prior malignancy not in complete remission or
clinically signicant systemic illness; and central nervous system metas-
tases (SS and MRCLS only). Primary endpoints: safety (adverse events)
and tolerability (dose-limiting toxicities). Secondary endpoints: investiga-
tor-assessed overall response rate, duration of response, and cell kinetics.
Results: e substudies are enrolling.
Discussion: Presented at AACR ’21 and ASCO ‘21. Funding: GSK
(209012; NCT04526509).
Conclusion: is master protocol will evaluate the safety and ecacy of
next generation NY-ESO-1 specic TCR-T cells in SS/MRCLS or NSCLC.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 55
730
Antitumor activity of dostarlimab in patients with advanced
or recurrent mismatch repair–decient or –procient cancer
by prior therapy: Results from the GARNET study
Lars Hanker1; Ana Oaknin2; Lucy Gilbert3; Anna Tinker4; Jubilee Brown5;
Cara Matthews6; Joshua Press7; Renaud Sabatier8; David O’malley9;
Vanessa Samouelian10; Valentina Boni11; Linda Duska12;
Sharad Ghamande13; Prafull Ghatage14; Rebecca Kristeleit15;
Charles Leath III16; Jennifer Veneris17; Tao Duan17; Ellie Im18;
Bhavana Pothuri19
1Universitatsklinikum Schleswig-Holsetin, Lübeck, Deutschland
2Vall dHebron University Hospital, Barcelona, Spanien
3McGill University Health Centre Research Institute, Montreal, Kanada
4BC Cancer, Vancouver, Kanada
5Levine Cancer Institute, Atrium Health, Charlotte, USA
6Women and Infants Hospital of Rhode Island, Providence, USA
7Swedish Cancer Institute, Gynecologic Oncology and Pelvic Surgery,
Seattle,USA
8Institut Paoli Calmettes, Marseille, Frankreich
9The Ohio State University James CCC, Columbus, USA
10Université de Montréal, Montreal, Kanada
11Hospital Universitario HM Sanchinarro, Madrid, Spanien
12Emily Couric Clinical Cancer Center, Charlottesville, USA
13Augusta University, Augusta, USA
14University of Calgary, Calgary, Kanada
15University College London, London, Vereinigtes Königreich
16University of Alabama at Birmingham, Birmingham, USA
17GlaxoSmithKline, Waltham, USA
18GlaxoSmithKline (when study was conducted), Waltham, USA
19New York University, New York, USA
Background: Dostarlimab is a humanized programmed death 1 (PD-1)
receptor monoclonal antibody that blocks interactions with PD-1 ligands.
GARNET (NCT02715284) is a phase 1 study assessing antitumor activity
and safety of dostarlimab monotherapy in patients with advanced solid
tumors.
Methods: is multicenter, open-label, single-arm study is conducted in
2 parts: dose escalation and expansion. Patients with advanced or recur-
rent mismatch repair–decient (dMMR) or microsatellite instability–
high (MSI-H) endometrial cancer (EC) or mismatch repair–procient
(MMRp) EC that progressed on or aer a platinum regimen received
dostarlimab 500 mg intravenously Q3W for 4 cycles, then 1000 mg Q6W
until disease progression or discontinuation. Primary endpoints were
objective response rate (ORR) and duration of response by BICR using
RECIST v1.1. Here we report ORR in dMMR/MSI-H and MMRp EC by
prior lines of therapy (LOTs).
Result: Ecacy analyses included 108 dMMR/MSI-H and 142 MMRp
patients. ORR (95% condence interval [CI]) was 43.5% (34.0–53.4) in
dMMR/MSI-H and 13.4% (8.3–20.1) in MMRp. ORR was slightly higher
(47.8%; 95% CI: 35.6–60.2) in patients with dMMR/MSI-H with 1 prior
LOT (n=69) but lower (35.9%; 95% CI: 21.2–52.8) in those who received
≥2 prior LOTs (n=39). In the MMRp population, ORR was 13.8% (6.5–
24.7) in patients with 1 prior LOT (n=65) and 13.0% (6.4–22.6) in patients
with ≥2 prior LOTs (n=77).
Safety has been previously reported.1
Discussion:
Conclusion: Dostarlimab demonstrated antitumor activity in recurrent
or advanced dMMR/MSI-H and MMRp EC regardless of number of prior
LOTs. Patients with dMMR/MSI-H EC who received 1 prior LOT had
slightly higher ORR than those who received ≥2 prior LOTs.
Reference:
1. Oaknin A, et al. Ann Oncol 2020;31(suppl 4):S1142–S1215
is abstract was previously presented at the International Gynecologic Cancer
Society 2021 Annual Meeting and is submitted on behalf of the original authors
with their permission.
Funding: GSK 213346; editorial support from Fishawack Indicia Ltd., UK, part of
Fishawack Health and funded by GSK.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
Endocrine Tumors (e. g. thyroid cancer, adrenal tumor, neuroendocrine tumor)
Poster
277
Selpercatinib ecacy and safety in patients with RET-altered
thyroid cancer: a clinical trial update
Eric Sherman1; Lori Wirth2; Manisha Shah3; Maria Cabanillas4; Bruce
Robinson5; Antoine Italiano6; Janessa Laskin7; Vivek Subbiah4; Alexander
Drilon8; Jennifer Wright9; Pearl French9; Victoria Soldatenkova9;
MatthiasKroiss10; Daniela Weiler11
1Memorial Sloan Kettering Cancer Center
2Massachusetts General Hospital, Boston, USA
3Ohio State University Comprehensive Cancer Center, Columbus, USA
4University of Texas M.D. Anderson Cancer Center, Houston, USA
5Royal North Shore Hospital, St. Leonards, Australien
6University of Bordeaux, Bordeaux, Frankreich
7British Columbia Cancer Agency, Vancouver, Kanada
8Memorial Sloan Kettering Cancer Center, New York, USA
9Eli Lilly and Company, Indianapolis, USA
10Universitätsklinikum Würzburg, Würzburg, Deutschland
11Cantonal Hospital, Luzern, Schweiz
Background: We report an update of selpercatinibs (a highly selective and
potent RET kinase inibitor) ecacy and safety results in RET-altered thy-
roid cancer, with a longer follow-up (30-Mar-2020 data cuto vs 16-Dec-
2019) and additional enrolment.
Methods: Patients (pts) with RET-mutant medullary thyroid cancer
(MTC) and RET-fusion positive thyroid cancer (TC) were enrolled in
global (16 countries, 89 sites) Phase 1/2 LIBRETTO-001 trial. Primary
endpoint: objective response rate (ORR). Secondary endpoints included
duration of response (DoR), progression-free survival (PFS), clinical ben-
et rate (CBR; CR+PR+SD ≥16 weeks) and safety. e integrated analysis
set (IAS, n=143) includes ecacy evaluable MTC pts previously treated
with cabozantinib and/or vandetanib (cabo/vande). e primary analysis
set (PAS), a subset of IAS, is the rst 55 enrolled pts. Cabo/vande naïve
MTC pts (N=112) and TC pts with prior systemic treatment (N=22) were
also analyzed. Safety population includes all pts who received ≥1 dose
(MTC N=315; TC N=42) by data cuto.
Result: For MTC patients, ORR% (95%CI) was 69.2 (61.0, 76.7) for IAS
(n=143), 69.1 (55.2, 80.9) for PAS (n=55) and 71.4 (62.1, 79.6) for cabo/
vande-naïve MTC pts (n=112). ORR% (95%CI) for TC pts (n=22) was
77.3 (54.6, 92.2). Most treatment-emergent adverse events (TEAEs) were
low grade; most common (≥25% MTC and/or TC pts treated with selp-
ercatinib) were dry mouth, diarrhea, hypertension, fatigue and constipa-
tion for both MTC and TC pts, increased ALT/AST, peripheral edema
and headache in MTC pts and nausea in TC pts. 4.8% MTC and TC pts
discontinued selpercatinib due to TEAEs; only 1.9% with MTC and none
with TC discontinued due to treatment-related adverse events.
Discussion: Selpercatinib continues to show marked and durable antitu-
mor activity in pts with RET-altered thyroid cancers. It is well tolerated
and no new safety concerns are identied.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts56
Conclusion: A global, randomized, phase 3 trial (LIBRETTO-531) eval-
uating selpercatinib vs cabo/vande in kinase inhibitor-naïve MTC pts is
ongoing.
Disclosure Statement: e authors declare the following: Vortragshonorar Lilly
Deutschland GmbH (persönlich bzw. Institution) Beraterhonorare Lilly Deutsch-
land GmbH Prüfer in klinischen Studien zu Selpercatinib LOXO Oncology
(Libretto-001-Studie) LOXO at Lilly (Libretto-201-Programm) Lilly (Libret-
to-531-Studie)
403
Mechanisms of CUX1-induced Tumor Progression in
Neuroendocrine Tumors of the Pancreas
Maryam Khosravian1; Stefanie Göllner1; Julia Weißbach1; Danny Misiak2;
Helmut Laumen1; Patrick Michl1; Sebastian Krug1
1University Hospital Halle (Saale), Department of Internal Medicine I, Martin
Luther University Halle-Wittenberg, Halle (Saale), Deutschland
2Department for Molecular Cell Biology, Institute for Molecular Medicine, Martin
Luther University Halle-Wittenberg, Charles-Tanford-Proteinzentrum, Halle
(Saale), Deutschland
Background: Pancreatic neuroendocrine tumors (PanNET) are a group
of heterogeneous malignancies. We previously identied the transcrip-
tion factor Cut homebox 1 (CUX1) as an important mediator of tumor
progression and therapy resistance in PanNET. Based on our preliminary
data, the aim of this work is to characterize the underlying molecular
mechanisms of CUX1-induced tumor progression to identify potential
targets for therapeutic intervention.
Method: In the two PanNET cell lines BON-1 and QGP1 transient CUX1
knockdown was performed by transfecting cells with siRNAs. For stable
knockdown, CUX1 oligonucleotides corresponding to gene specic small
hairpin RNA sequences were cloned into the pGreenPuro lentivector.
e CUX1-p200 gene was cloned into the pCDH overexpression vector.
Western blotting assay was used to investigate CUX1 expression levels. To
assess eect on apoptosis, TUNEL assay was used. RNA sequencing was
performed to provide insight into the transcriptome of PanNETs. To fur-
ther characterize the impact of CUX1 KD, gene set enrichment analysis
(GSEA) based on sequencing data was accomplished.
Result: Transiently CUX1 KD in PanNET cells showed an upregulation
of apoptosis. e RNA sequencing data displayed numbers of mRNAs,
lncRNAs and miRNAs, which are dierentially expressed (FDR < 0.05)
upon CUX1 KD. STC1, LINC02404 and hsa-miR-1197 are interesting
candidates that are upregulated with CUX1 KD. GSEA identied E2F tar-
gets, G2M checkpoint as well as MYC targets as top depleted and hypoxia,
oxidative phosphorylation and TNFA signaling as top-enriched pathways
in CUX1 KD cells.
Discussion and conclusion: Our results suggest that CUX1 could behave
as an oncogenic factor in PanNET via modulating a complex network of
protein-coding and non-coding RNAs. Further experiments such as mass
spectrometry, lncRNA pull down and miRNA knockdown are needed to
elucidate the mechanisms in detail and to propose targets for therapeutic
intervention in CUX-1 overexpressing PanNET.
Disclosure Statement: e authors declare no conict of interest.
579
Papillary thyroid cancer and its neoplastic variants –
connection with the genomic prole, cyto/hystopathological
ndings and clinical presentation
Darko Katalinic1; Ivan Aleric1; Aleksandar Vcev1; Ante Škaro2;
Irena Ranogajec3
1Faculty of Dental Medicine and Health and Faculty of Medicine, J.J. Strossmayer
University, Osijek, Kroatien
2Leptir Clinic, Zagreb, Kroatien
3Sveti Duh Clinical Hospital, Zagreb, Kroatien
Background: Papillary thyroid cancer (PTC) accounts for approximately
80% of all thyroid cancers and is dened by its unique cytologic and his-
tologic features. Mutations of the RET and BRAF/V600 genes are found
in nearly 70% of PTC cases. ey are able to trigger the activation of
mitogen-activated protein kinase pathway and to promote neoplastic cell
proliferation. Genetic events may further lead to numerous dierent cell
variants of PTCwhich may be identied via the dierent cyto/histopatho-
logic features. e most common are the classical (CV), tall cell (TCV)
and follicular variant (FV). e aim of the study was to perform the geno-
myc analysis of the RET and BRAF(V600) mutations as well as to compare
the obtained results with clinical ndings.
Methods: e study included 112 patients, aged 49-74 years. Mutations
of the RET and BRAF(V600) genes were detected using Real-time poly-
merase chain reaction. Diagnosis of the PTC and its variants was con-
rmed with cyto/histopathological examination.
Result: e most important genomic, cyto/histopathological and prog-
nostic elements regarding all three variants of the PTC: CV-PTC (n=78):
RET and BRAF(V600) mutations are common ndings, with BRAF(V600)
conrming a worse prognosis. e 65% of these patients have shown sta-
bile disease course, with25% with metastatic nodes; TCV-PTC (n=8):
Aggressive behavior has been attributed to BRAF(V600) mutation.
FV-PTC (n=26): Absence of BRAF(V600) mutation was the most import-
ant genetic element.
Discussion: PTC has an excellent prognosis, but certain variants express
more aggressive clinical course. CV-PTC: BRAF(V600) mutation was neg-
ative prognostic element. TCV-PTC presents mostly in older patients, has
a greater propensity for locoregional dissemination and has more aggres-
sive course than CV-PTC; e prognosis of FV-PTC has been similar to
that of CV-PTC.
Conclusion: Our study suggests that PTC is etiopathogenically complex
disease and requires further molecular investigations. e patients with
CV-PTC and FV-PTC had fovorable clinical course comparing to those
with TCV-PTC.
Disclosure Statement: e authors declare no conict of interest.
781
Rare coincidental diagnosis of simultaneous isolated
extrapulmonary sarcoidosis and low-grade thyroid carcinoma
Frank Meyer; Roland S. Croner; Manuela Petersen
Dept. of General, Abdominal, Vascular and Transplant Surgery, Otto-von-
Guericke University at Magdeburg with University Hospital, Magdeburg,
Deutschland
Background: Sarcoidosis is a rare granulomatous multi-locular, systemic
disease of not completely known etiopathogenesis with substantial het-
erogeneity. Typically, it is associated with the lung, but can become man-
ifest in various organs.
Aim: To illustrate the rare constellation of a simultaneous isolated
extrapulmonary sarcoidosis in the thyroid gland & a poorly dierentiated
thyroid carcinoma
Methods: Scientic case report - data was obtained from routine medical
records.
Result: A 30-years old woman presented with progressive swelling at the
right neck & increased serum thyroglobulin (632 ng/mL). Ultrasonically,
an inhomogeneous node (size, 37x30x35 mm) of the right thyroid gland
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 57
with echo-poor parts & peripheral vascularization was seen; scintigra-
phy showed marginally compensated unifocal autonomy of the thyroid
gland. Right hemithyroidectomy conrmed a nodous structure of thyroid
parenchyma w/o suspicious lymph nodes. Histologically, a 33mm follic-
ular, nodular, encapsulated structure of thyroid parenchyma diagnosed
as follicular adenoma was rst described. External pathological review
reclassied this structure as poorly dierentiated carcinoma of the thyroid
gland with angio-inltrating growth & granulomatous inammation of
sarcoidosis type. According to tumor-board recommendation, complet-
ing thyroidectomy was performed with subsequent ablative radioactive
iodine therapy. Final tumor characteristics were pT2 pN0(0/1) V1 L0 G3
R0. 18F-FDG-PET-CT scan & bronchoscopy showed no further manifes-
tation of sarcoidosis.
Discussion: Extrapulmonary manifestations of sarcoidosis can occur
both w/ & w/o pulmonary manifestation. e simultaneous occurrence of
a thyroid carcinoma & an isolated sarcoid of the thyroid has not yet been
described in the literature.
Conclusion: Incidental ndings of extrapulmonary granulomas should
result in further investigation to identify additional manifestations & to
exclude orid infection or other granulomatous processes. erapy is only
indicated in symptomatic organ manifestations.
Disclosure Statement: e authors declare no conict of interest.
Epidemiology
Best-of-Abstract-Vortrag
452
Inuence of the COVID-19 pandemic on the incidence, stages
and treatment of cancer
Elisabeth C. Inwald1; Michael Gerken2,3; Armin Pauer2,3;
Monika Klinkhammer-Schalke2,3; Olaf Ortmann1
1University Medical Center Regensburg, Department of Gynecology and
Obstetrics, Regensburg, Deutschland
2Tumour Center, Institute for Quality Management and Health Services
Research, University of Regensburg, Regensburg, Deutschland
3Bavarian Cancer RegistryRegional Centre Regensburg, Bavarian Health and
Food Safety Authority, Regensburg, Deutschland
Background: e eects of the COVID-19 pandemic on incidence, stage
distribution, primary therapy, and delay in therapy were analyzed for
breast cancer, prostate cancer, colorectal cancer, bronchial cancer, lym-
phoma and leukemia.
Methods: e years 2020 versus 2019 were compared with focus on the
months of the rst wave of pandemics from February to May 2020 analyz-
ing data from the clinical cancer registry Regensburg.
Result: e total numbers of annual new cases were lower in all entities in
2020 vs. 2019. e percentage decrease ranged between -1.9% for breast
cancer and -15.3% for colorectal cancer, with highly signicant dierence
for colorectal cancer (p<0.001). e comparison of the monthly reported
number of cases showed a decrease in all analyzed cancer entities, in
March to May 2020 compared to 2019 with statistical signicance. ere
was no signicantly increased rate of patients with advanced stages III/IV,
larger tumors T3/T4, positive node status or distant metastases in nearly
all entities neither in the annual nor the monthly comparison. Colorectal
cancer was an exception, with signicantly increased rates in March and
April 2020. Apart from bronchial cancer, rates of primary therapy in
stages I-III in 2020 were mostly slight, but not signicantly lower than in
2019. Signicantly lower treatment rates were found for prostate cancer
in March 2020 and for colorectal cancer in November 2020. e mean
interval between diagnosis and start of therapy was the same or slightly
longer in 2020, but not signicant, except for lung cancer, leukemia and
lymphoma.
Discussion: A potential lack in transmitted medical informations, a delay
of documentation and consequently restricted real-time analysis must be
considered when using data from clinical cancer registries.
Conclusion: A decreased incidence especially during the rst wave
could be shown. A shi of stage distribution and treatment delay was not
observed. Follow-up analyses and observation of the subsequent pan-
demic waves are necessary to conrm the current results.
Disclosure Statement: e authors declare no conict of interest.
Poster
531
Eectiveness of Care in Certied Cancer Centers (WiZen) -
Success of Data Linkage between SHI and Clinical Cancer
Registries
Christoph Bobeth1; Kees Kleihues-van Tol2; Martin Rößler1;
Veronika Bierbaum1; Michael Gerken3; Christian Günster4;
Patrik Dröge4; Thomas Ruhnke4; Monika Klinkhammer-Schalke2,3;
Jochen Schmitt1; Olaf Schoer1
1Universitätsklinikum Carl Gustav Carus Dresden, Zentrum für Evidenzbasierte
Gesundheitsversorgung (ZEGV), Dresden, Deutschland
2Arbeitsgemeinschaft Deutscher Tumorzentren e.V., Berlin, Deutschland
3Tumorzentrum Regensburg, Regensburg, Deutschland
4Wissenschaftliche Institut der AOK (WIdO), Berlin, Deutschland
Background: e project “Eectiveness of care in certied cancer cen-
ters” (WiZen), funded by the Innovation Fund, explores certications in
oncology. e project uses nationwide data from SHI and clinical cancer
registries from four states covering the years 2006-2017. To combine the
strengths of both data sources these are linked for eight dierent cancer
entities in accordance with data protection regulations.
Methods: Data linkage was performed using indirect identiers and vali-
dated using the health insurance ID number as a direct identier and gold
standard. is allowed for quantication of the potential and quality of
dierent linkage variants. Sensitivity and specicity as well as matching
accuracy and precision were used as criteria for the evaluation of the link-
age alternatives. e distributions of relevant variables resulting from the
linkage were validated against the original distributions in the individual
datasets.
Result: Depending on the combination of indirect identiers, the range
of linkage matches was 19,854 to 1,860,145. Near-perfect indirect linkage
of the considered data was achieved by combining information on entity,
date of birth, gender, and zip code of the patients. A total of 62,868 one-
to-one linkages were achieved with the above characteristics and a median
hit quality of more than 97% related to the gold standard for the entities.
e age and sex distributions of the various data sources also showed a
high degree of agreement.
Discussion: SHI and cancer registry data can be linked with high inter-
nal and external validity at the level of the individuals. e stable linkage
allows for entirely new analyses due to simultaneous access to variables
from both data sets (“the best of both worlds”): For individual patients,
both information on UICC stage of disease from the registries and comor-
bidities from SHI data are now available.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts58
Conclusion: Due to the use of readily available linkage variables and the
high success of assignment, our linkage has model character for future
linkage methods in health services research.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organiser KUKM GmbH and KUKM
can disclose them if needed.
612
Secondary immunodeciency diagnosis in patients with
oncological diseases in Germany
Karsten Franke1; Manfred Welslau2; Christoph Hirche3; Stephan Kaiser3;
Christian Schindler4; Dennis Häckl4
1Institut für Klinische Immunologie, Marien Kliniken Siegen, Siegen, Deutschland
2Onkologisches Zentrum Aschaenburg, Klinikum Aschaenburg-Alzenau,
Aschaenburg, Deutschland
3Takeda Pharma Vertrieb GmbH & Co. KG, Berlin, Deutschland
4WIG2 GmbH, Leipzig, Deutschland
Background: Severe or recurring infections are a common complication
in immunocompromised patients. While a primary immunodeciency
(PID) can be the cause, signicantly more patients suer from a second-
ary immunodeciency ((SID) due to certain underlying diseases) and its
treatments. is claims data analysis describes the prevalence of SID in
the German statutory health insurance (SHI) system and investigates SID
in the subset of patients with specic oncological diseases (e.g. multiple
myeloma (MM) or chronic lymphocytic leukemia (CLL)).
Methods: We used German SHI claims data from almost 4 million patients
from 2013 to 2019. To investigate the prevalence of SID, we selected
patients with certain underlying diseases and included those with ICD-
10-GM codes for immunodeciency proposed by [1], following diagno-
sis of the underlying condition. e analyzed subset of cancer patients
included patients diagnosed with ICD-10 C81 – C92. For incidence and
prevalence evaluation coding of immunodeciency aer diagnosis of the
oncological disease was required.
Results: Extrapolated to the German SHI population, 25,686 patients had
SID in 2019, with prevalence slightly increasing over time. Around 41.5%
of SID patients suered from an underlying oncological disease (e.g.
19.2% had CLL, 12.0% had MM).
SID coding was strikingly low: only 4.4% of the selected cancer patients
had an SID diagnosis, while 33.8% had at least one severe or at least three
recurring infections within four consecutive quarters.
Discussion: Severe or frequently recurring infections occur in more than
one third of all cancer patients. However, secondary immunodeciency is
rarely diagnosed and may result in patients not receiving guideline-ade-
quate care.
Conclusion: SID appears to be underdiagnosed in cancer patients, demon-
strating the need for improved diagnostics and therapeutic strategies.
Indication of source:
1. Zi Zentralinstitut für die Kassenärztliche Versorgung in Deutschland (2020).
Zi-Kodier-Manual Infektanfälligkeit und Immundefekt.
Disclosure Statement: e authors declare the following: Wirtschaliche
Verbindungen
618
Gastroenteropancreatic neuroendocrine neoplasms –
site-specic trends in Bavaria, Germany
Nina Grundmann; Amir Hakimhashemi; Sven Voigtländer; MartinMeyer;
Jacqueline Müller-Nordhorn
Bayerisches Krebsregister, Bayerisches Landesamt für Gesundheit und
Lebensmittelsicherheit (LGL), Nürnberg, Deutschland
Background: Neuroendocrine neoplasms (NEN) are rare and heteroge-
neous tumours, occurring throughout the body. Treatment and prognosis
are mainly determined by NEN localization and histology. Forgastroen-
teropancreatic (GEP) NEN, rising incidence rates were reported for the
last decades, with underlying causes remaining largely unexplained.
Methods: Incident cases of GEP NEN diagnosed between 2005 and 2019
were retrieved from the Bavarian Cancer Registry and stratied for neu-
roendocrine tumours (NET) and neuroendocrine carcinoma (NEC). We
calculated age-standardized incidence rates for all GEP NEN localizations
(International Classication of Diseases, Tenth Revision (ICD-10), codes
C15-C25) and used an annual percentage change (APC) approach includ-
ing a joinpoint analysis to investigate site- and sex-specic trends.
Result: Over the study period, we observed a strong increase of inci-
dence rates for GEP NEN until 2012 (APC 2005-2012: 10.0%) followed
by a slight rise aerwards (APC 2012-2019: 1.8%). Age-standardized rates
of GEP NEN rose from 2.2/100,000 in 2005 up to 4.8/100,000 in 2019.
e increase was mainly driven by the rise of NET from 2008 onwards
(APC 2005-2008: -12.9%; APC 2008-2012: 34.3%; APC 2012-2019: 6.8%).
In contrast, NEC incidence rates rose from 2005 to 2010 (APC: 12.1%)
and decreased from 2010 to 2019 (APC: -7.3%). e highest increase
of NEN incidence rates was found for the stomach (APC: 7.6%; from
0.3/100,000 in 2005 to 0.6/100,000 in 2019) and the pancreas (APC: 7.1%;
from 0.4/100,000 to 1.2/100,000, respectively). NEN rates also rose in the
appendix, the rectum and the small intestine. Trends were similar for men
and women.
Discussion: Continuously rising incidence rates of GEP NEN indicate
an increase in the burden of NEN. However, this increase may partially
be attributable to an increased use of advanced imaging techniques and
endoscopic procedures.
Conclusion: Further research including stage-specic analyses is needed
to better understand trends in NEN incidence.
Disclosure Statement: e authors declare no conict of interest.
639
Modeling age-specic incidence of colon cancer via niche
competition
Steen Lange; Richard Mogwitz; Denis Huenniger; Anja Voß-Böhme
Hochschule für Technik und Wirtschaft Dresden (HTW Dresden), Fakultät
Informatik/Mathematik, DataMedAssist, Dresden, Deutschland
Background: Cancer development is a multistep process oen starting
with a single cell turning into a tumor cell due to genetic and epigene-
tic alterations, whose progeny growths via clonal expansion into a mac-
roscopic tumor with billions of cells. While experimental insight exists
on the cellular scale and cancer registries provide statistics on detectable
tumors, the complex dynamics leading from the microscopic cellular scale
to a macroscopic tumor is still not fully resolved. e study ‚Modeling
age-specic incidence of colon cancer via niche competition‘ aims to con-
nect these to two regimes of cancer development.
Methods: We use a cell-based Moran model, which focuses on the com-
petition between wild-type and tumor cells in colonic crypts, to repro-
duce epidemilogical age-specic incidence rates of colon cancer fom the
SEER database. All model parameters are directly set by known physio-
logical parameters and only the eective replacement rate in the crypt is
calibrated.
Result: e model predictions match the epidemilogical rates, even at
ages below 30, where rates are orders of magnitude smaller. e model
predictions are also consistent with the common clinical estimates that
more than 95% of colon adenocarcinomas arise from colonic polyps and
that the fraction of benign tumor is over 99%. Model prediction and epi-
demiological incidence rates agree analogously for rectal cancer.
Discussion: In contrast to previous models, which require four or more t
parameters to reproduce epidemiological incidence rates, our model only
requires a single time scale to be calibrated.
Conclusion: e predictive power of the pretumor progression model
strongly suggests that the fate of tumor development is dominated by
the early phase of tumor development long before a tumor becomes
detectable.
Disclosure Statement: e authors declare no conict of interest. e authors
work at a technical college and the work is co-funded by the EU, the European
Social Fund (ESF) and by tax funds on the basis of the budget passed by the
Saxonstate parliament.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 59
675
Municipal solid waste landll sites and cancer risk in Germany
Isabelle Finke, Stephanie Aker, Soo-Zin Kim-Wanner
Hessisches Krebsregister, Hessisches Landesprüfungs- und Untersuchungsamt
im Gesundheitswesen, Frankfurt am Main, Deutschland
Background: e possible cancer risk of exposures associated with solid
waste landll sites is under continuous discussion. Reliable evidence is
sparse, as analyses require many covariates from diverse data sources and
long-term observations. e present study aimed to rst give a systematic
overview of recent research on cancer risk close to landll sites and sec-
ond to point out and compare the current research situation available for
Germany.
Methods: We conducted a literature search according to PRISMA guide-
lines by using the Medline database PubMed. Studies were included if
they reported on exposure to residents living in closer proximity to land-
ll sites and cancer risk either dened as incidence or mortality. e focus
was on publications reporting on German data. Furthermore, a review and
comparison of international studies and available data were performed.
Result: e literature search showed that very few studies have been
published including German data. One German study was found inves-
tigating on the landll site „Ihlenberg“ which reported a higher cancer
incidence for occupational exposure but not for the cohort of residents
[1]. Few studies from other countries reported higher cancer mortality,
especially lung cancer but evidence was mostly inadequate due to study
quality. Most studies were conducted 15 years ago or older, mainly in
Europe, North America or Asia.
Discussion: e present review highlighted a lack of studies regarding
the association between residency in the proximity of landll sites and
cancer risk in the German context. Due to structural dierences of landll
sites between countries, it is dicult to transfer study results from other
countries to Germany.
Conclusion: Future research should ll this gap of knowledge for
Germany.
Indication of source:
1. Stefan Weiß, Wolfgang Homann. Epidemiologische Untersuchung zu
Tumorerkrankungen in der Umgebung der Deponie Ihlenberg (2009). URL:
http://www2.medizin.uni-greifswald.de/icm/index.php?id=357 (Accessed:
30.08.2021)
Disclosure Statement: e authors declare no conict of interest.
716
Uptake of NCCN-recommended care of patients diagnosed
with leading cancer entities in Sub-Saharan Africa – a
multinational, population-based cohort study 2009-2016
Nikolaus Mezger1, Tobias Paul Seraphin1, Robert Richter1, Mirko Griesel1,
Lucia Hämmerl1, Jana Feuchter1, Yvonne Walburga Joko-Fru2,3,
Anelle Zietsman2,4, Jean-Félix Péko2,5, Nathan Buziba2,6,
MaryNyanchama2,7, Cesaltina Lorenzoni Ferreira2,8,
Eva Johanna Kantelhardt1,9
1Institute of Medical Epidemiology, Biometrics and Informatics, Martin-Luther-
University Halle-Wittenberg, Halle (Saale), Deutschland
2The African Cancer Registry Network, INCTR African Registry Programme,
Oxford, Vereinigtes Königreich
3Nueld Department of Population Health, University of Oxford, Oxford,
Vereinigtes Königreich
4Dr AB May Cancer Care Centre, Windhoek Central Hospital, Windhoek, Namibia
5Registre des cancers de Brazzaville, Brazzaville, Congo
6Eldoret Cancer Registry, Moi Teaching and Referral Hospital, Eldoret, Kenya
7Kampala Cancer Registry, Makerere University School of Medicine, Kampala,
Uganda
8Departamento de Patologia, Faculdade de medicina, Universidade Eduardo
Mondlane, Hospital Central de Maputo, Maputo, Mozambique
9Department of Gynaecology, MartinLutherUniversity HalleWittenberg, Halle
(Saale), Deutschland
Purpose: We aimed to assess uptake of care concordant with NCCN
Iium gin from ow roportion of patients Harmonized Guidelines for Sub-
Saharan Africa (SSA).
Methods: Our observational study covered 11 population-based can-
cer registries in 10 countries. Per registry, random samples diagnosed
from 2010 to 2015 with leading entities were selected: breast (BCa),
cervical, prostate (PCa), colorectal cancer and non-Hodgkin lym-
phoma (NHL). Registry data were actively updated assessing hos-
pital records. Diagnostics and cancer-directed therapy (CDT) were
evaluated for degree of concordance to the NCCN Harmonized Guidelines.
Results: Of 3251 patients, records could be “traced” for 58%. Early and
advanced disease was found in 4, metastatic in 1 of 5. HIV infection was
found in 2 of 5 tested, and ECOG PS ≥ 2 in half of all assessed. Diagnostics
relevant for CDT were missing for a considerable proportion of patients,
e.g. Gleason score for half of PCa, hormone receptor status for 4 in 5 BCa,
and subtype for 6 in 10 NHL patients. Any CDT was identied in 2 of
3 traced. In patients eligible (n=906), guideline-concordant therapy was
found in 1 of 9, with deviations in 5, and no therapy in 2 of 9. Patients with
BCa and cervical cancer, early stage, low ECOG PS and medium HDI-
origin were more likely to access guideline concordant care.
Discussion: Cancer cases in SSA will rise up to one million by 2040 annu-
ally. ough many patients presented with potentially curable disease,
access to diagnostics and treatment was low compared to hospital-based
cohorts.
Conclusion: is real-world population-based data shows the need for
timely, quality assured and aordable oncology service. Our study informs
clinicians and policy-makers on overall and entity-specic opportunities
for improvement of cancer care in SSA.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts60
862
Prevalence and Treatment of patients with dierent types of
Non-Hodgkin Lymphoma in Germany
Karina Manz1; Valeria Weber1; Dorota Pawlowska-Phelan2; Ariane Höer1;
Anja Mocek1; Tina Ploner2; Heiko Schellhorn3
1IGES Institut GmbH, Berlin, Deutschland
2InGefInstitute for Applied Health Research Berlin GmbH, Berlin, Deutschland
3Roche Pharma AG, Grenzach-Wyhlen, Deutschland
Background: Little is known about the antineoplastic treatment of chronic
lymphocytic leukemia (CLL), follicular lymphoma (FL), and diuse large
B-cell lymphoma (DLBCL) in the German real world setting. Based on
German health claims data, we estimated the prevalence of CLL, FL, and
DLBCL and described the treatment of prevalent patients.
Methods: is retrospective cohort study was based on the Institute for
Applied Health Research Berlin (InGef) research database and covered the
years 2018 to 2020. Patients were identied based on documented ICD-10
diagnosis codes (C91.1 [CLL], C82 [FL], and C83.3 [DLBCL]). e treat-
ment was described by assessing the share of patients who received at least
one pre-dened disease-related therapy (combination or monotherapy)
during the respective year. erapy lines were not dierentiated.
Result: e estimates of the prevalence in 2020 were 0.13 % (CLL), 0.05
% (FL), and 0.04 % (DLBCL). In each condition, the prevalence increased
with age until peaking in 75-84 year-olds.
In 2020, the most commonly received therapies in prevalent CLL patients
were ibrutinib, mono (8.9 %), venetoclax, mono (2.7 %), and rituximab +
bendamustine (R-Benda) (1.8 %). From 2018 to 2020, the share of patients
who received R-Benda decreased.
In 2020, the rituximab-based therapies R-Benda and R-CHOP were
received by 3.2 and 0.9 % of FL patients, respectively. 5.1 % received obinu-
tuzumab, mono and 2.4 % obinutuzumab + bendamustine (G-Benda).
From 2018 to 2020, the share of FL patients who received obinutuzumab,
mono and G-Benda increased.
In 2020, R-Benda and R-CHOP were received by 2.7 and 2.9 % of DLBCL
patients, respectively.
Discussion: Our study provides recent estimates of the prevalence of CLL,
FL, and DLBCL, and insights into the treatment situation of prevalent
patients in Germany. e results must be interpreted within the limita-
tions of German health claims data.
Conclusion: is study may serve as a starting point for future longitudi-
nal analyses describing treatment pathways.
Disclosure Statement: e authors declare no conict of interest.
876
Spatial inequalities of tumour size at diagnosis in Germany:
An ecological study in eight federal states
Philipp Jaehn1,2; Andreas Bergholz1,2; Christine Holmberg1,2
1Institute of Social Medicine and Epidemiology, Brandenburg Medical School
Theodor Fontane, Brandenburg an der Havel , Deutschland
2Faculty of Health Sciences Brandenburg, Brandenburg Medical School Theodor
Fontane, Potsdam, Deutschland
Background: A place of residence with high socioeconomic deprivation,
low social capital, and a rural settlement structure is associated with an
advanced stage at cancer diagnosis in several international contexts, how-
ever, few studies have examined these characteristics in combination. We
aimed to assess the association of these spatial factors with primary tumor
size at diagnosis of selected cancer types in Germany.
Methods: All incident cases of female breast cancer, colorectal cancer,
malignant melanoma, uterine cancer, and male bladder cancer were
included. Cases were collected by epidemiological cancer registries
in eight German states between 2010 and 2014. e T-status was used
to dene an advanced tumor size at diagnosis. Sex-specic, mutually
adjusted associations of spatial characteristics with advanced tumor size
and intraclass correlation coecients (ICC) were estimated by multilevel
logistic regression at the level of administrative districts. Missing data on
tumor size were accounted for by multiple imputation.
Result: A total of 386,223 cases were included in this analysis. High spatial
socioeconomic deprivation was associated with an advanced tumor size
of colorectal cancer and malignant melanoma. For malignant melanoma,
low spatial social capital in women and men and a rural settlement struc-
ture in men were related with advanced tumor size. Meaningful ICCs were
found for malignant melanoma. No associations were identied for breast
cancer, uterine cancer, and bladder cancer.
Discussion: Limitations of this study include moderate proportions of
missing data on T-status and a high heterogeneity of regional character-
istics at the level of administrative districts. In contrast to results from
international studies, socioeconomic deprivation and rurality were not
associated with tumor size of breast cancer.
Conclusion: Spatial socioeconomic deprivation, spatial social capital, and
rurality are independent predictors of tumor size at diagnosis of malig-
nant melanoma.
Disclosure Statement: e authors declare no conict of interest.
906
WAYFIND-R: Delivering a high-quality real-world data (RWD)
global registry of patients diagnosed with a solid tumor and
proled with next-generation sequencing (NGS)
Christophe Le Tourneau1; Allan Hackshaw2; Jean-Yves Blay3; Jan Geissler4;
Clare Turnbull5; Camille Perret6; Olga Skatkova6; Martina von Meyenn6;
Rodrigo Dienstmann7
1Institut Curie, Paris cedex 05, Frankreich
2UCL Cancer Institute, London, Vereinigtes Königreich
3Centre Léon Bérard, Lyon, Frankreich
4Patvocates GmbH, Riemerling, Deutschland
5The Institute of Cancer Research , London, Vereinigtes Königreich
6F. Homann-La Roche Ltd, Basel, Schweiz
7Oncoclínicas Grupo, São Paulo, Brasilien
Background: NGS-based, molecularly guided therapy is becoming a
pivotal part of precision oncology. Rare molecular cancer subtypes pose
diculties in traditional clinical trials; collecting patient RWD can help
elucidate the eectiveness of targeted therapies, molecular tumor boards
(MTBs) and NGS-based genomic proling. WAYFIND-R (NCT04529122)
is a global registry that: 1) characterizes the treatments and clinical course
of patients with cancer; 2) provides a data research platform to evaluate
real-world treatment decisions and outcomes; 3) supports the design/con-
duct of epidemiological research and clinical trials. WAYFIND-R will pro-
vide key learnings on data quality, sharing, and privacy for contemporary
disease registries.
Methods: WAYFIND-R is a prospective registry with longitudinal,and
standardized data collection to enhance data quality and minimize miss-
ing data. WAYFIND-R includes adults with any type/stage of solid tumor
proled with NGS. NGS details, patient sociodemographics, cancer char-
acteristics, patient-relevant safety data, treatment decisions, and outcomes
are collected at baseline and prospectively every ≤6 months. By 2026,
WAYFIND-R aims to enroll ~15,000 patients in ≥35 countries.
Result: As of April 2022 154 patients have been enrolled.
Discussion: A key component is the potential to explore global and
local data within a secure analytics platform, accessed through a visual
dashboard to nd treatment decisions for similar patients elsewhere.
Researchers can access the patient-level dataset for correlative analyses,
aer independent data access committee approval. WAYFIND-Rs meth-
odological/operational aspects were guided by external experts and the
European Medicines Agency.
Conclusion: WAYFIND-R will inform on best practice for NGS-based
treatment decisions by clinicians, foster global collaborations between
cancer centers , aid understanding of disparities in patients’ access to
advanced diagnostics and therapies, and ultimately drive advances in pre-
cision oncology.
Pres. by AACR 2022
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 61
916
Conceptualization of core clinico-molecular variables for
registries enrolling patients diagnosed with a solid tumor and
proled with next-generation sequencing (NGS)
Rodrigo Dienstmann1; Clare Turnbull2; Allan Hackshaw3; Jean-Yves Blay4;
Maud Kamal5; Nicolas Servant5; Jan Geissler6; David Tamborero7;
Janick Weberpals8; Simon Fear8; Camille Perret8; Laura Perez8,
Martina von Meyenn8; Christophe Le Tourneau5
1Oncoclínicas Grupo, São Paulo, Brasilien
2The Institute of Cancer Research , London, Vereinigtes Königreich
3UCL Cancer Institute, London, Vereinigtes Königreich
4Centre Léon Bérard, Lyon, Frankreich
5Institut Curie, Paris, Frankreich
6Patvocates GmbH, Riemerling, Deutschland
7Karolinska Institutet , Stockholm, Schweden
8F. Homann-La Roche Ltd, Basel, Schweiz
Background: In precision oncology, tailored treatment decisions are
largely driven by genomic alterations in a patients tumor. To support
epidemiological research we initiated a registry that enrolls patients diag-
nosed with a solid tumor and proled with NGS. Collecting and stan-
dardizing variables of interest across the patient journey is critical for
data harmonization and understanding clinical relevance. We propose
a framework for identifying core variables most critical for solid tumor-
based, real-world data studies and registries in precision oncology.
Methods: A patient representative and panel of experts in oncology, epi-
demiology, bioinformatics and molecular pathology was assembled to
compile a dra variables list. To reduce the burden of data collection and
missingness, the variables were categorized by decreasing importance and
reconciled with dra European Medicines Agency guidelines on regis-
try-based studies. If applicable internationally harmonized coding dictio-
naries were used to standardize the variables.
Result: e dra list comprised ~500 variables and was reconciled to
~150; highest priority was given to patient information, NGS test results
(e.g. actionable alterations, genomic signatures), cancer details (e.g.
disease ontology, staging, metastases), and therapy details/outcomes.
Variables with moderate to lower priority comprised NGS (e.g. technical,
quality criteria), familial cancer history, adherence to molecular tumor
board recommendations, and primary cause of death.
Discussion:e variable list was created to: describe a patients cancer his-
tory and journey eectively; allow conduct of comparative eectiveness
studies and comparisons with clinical trials; and represent key risk factors
or important confounders for prognosis or statistical analysis adjustments.
Conclusion: is list provides viable guidance for conducting research-
and regulatory-grade real-world data-based precision oncology studies,
and facilitating standardized data collection and thus pooling from var-
ious datasets.
Pres at AACR 2022
Disclosure Statement: e authors declare the following: Advisory Board: BMS,
Roche, Sano-Aventis, GSK, Novartis, Pierre Fabre, Guardant Health
970
Overall and country-specic agreement in symptom
reporting between prostate cancer patients and healthcare
professionals in the international multicentre REQUITE study
Philipp Heumann1,2; Irmgard Helmbold1; David Azria3; Erik Briers4;
Ananya Choudhury5; Dirk De Ruysscher6,7; Marie-Pierre Farcy-Jacquet8;
Tiziana Rancati9; Barry Rosenstein10; Elena Sperk11; Christopher Talbot12;
Ana Vega13; LIV Veldeman14; Tim Ward15,16; Adam Webb12;
Catharine West17; Jenny Chang-Claude1,18
1German Cancer Research Center (DKFZ), Heidelberg, Deutschland
2Johannes Gutenberg University Mainz, Mainz, Deutschland
3Montpellier Cancer Institute, Montpellier, Frankreich
4Patient advocate, Hasselt, Belgien
5Christie Hospital, University of Manchester, Manchester, Vereinigtes Königreich
6Maastro Clinic, Maastricht, Niederlande
7KU Leuven, Leuven, Belgien
8CHU Nimes, Nimes, Frankreich
9Istituto Nazionale dei Tumori, Milan, Italien
10Icahn School of Medicine at Mount Sinai, New York, USA
11Medical Faculty Mannheim, University of Heidelberg, Mannheim, Deutschland
12University of Leicester, Leicester, Vereinigtes Königreich
13Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela,
Spanien
14Ghent University Hospital, Ghent, Belgien
15Trustee Pelvic Radiation Disease Association, Vereinigtes Königreich
16NCRI CTRad Consumer, Vereinigtes Königreich
17University of Manchester, Manchester, Vereinigtes Königreich
18University Cancer Center Hamburg, University Medical Center
Hamburg-Eppendorf, Hamburg, Deutschland
Background: Previous studies showed that healthcare professionals and
patients had only moderate to low agreement on their assessment of treat-
ment-related symptoms. Here we aimed to determine the levels of agree-
ment in a large cohort of prostate cancer patients.
Methods: Analyses were made of data from 1756 prostate cancer patients
in seven European countries and the USA treated with external beam
radiotherapy (RT) and/or brachytherapy and recruited into the pro-
spective multicentre cohort REQUITE study (www.requite.eu). Eleven
pelvic symptoms at the end of RT were compared aer translating patient-
reported outcomes (PROs) into CTCAE based healthcare professional
ratings. Gwet’s AC2 agreement coecient was calculated across countries
and country-specically for each symptom. To compare severity of grad-
ing between patients and healthcare professionals, percent agreement and
deviations for each symptom were examined.
Result: Across countries, agreement was very good (haematuria, rectal
bleeding, management of sphincter control) or good (diarrhoea, erectile
dysfunction, urinary incontinence) for 6 of 11 symptoms. Libido/ orgasmic
dysfunction and urinary retention showed moderate whereas urinary fre-
quency fair, proctitis and urinary urgency poor agreement. More observ-
able symptoms with few symptomatic patients such as haematuria and
rectal bleeding showed little between-country variation in agreement.
For subjective symptoms such as proctitis, considerable dierences were
observed between countries, ranging from poor to good agreement.
Discussion: Agreement was better for more observable than subjec-
tive symptoms, with patients tending to grade their symptoms more
severely. Between-country dierences in levels of agreement varied across
symptoms
Conclusion: PROs should complement symptom assessment by health-
care professionals and be taken into consideration for clinical decision-
making to incorporate the patient perspective. Parts of this analysis were
presented at the 2022 Congress of the German Society for Epidemiology.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts62
Gastrointestinal (Colorectal) Cancer
Best-of-Abstract-Vortrag
583
PFKFB3 inhibition by 3PO as a therapeutic target in colorectal
cancer
Marcus Edelmann1; Shuang Fan1; Tina Goldhardt1; Karly Conrads2;
TimBeissbarth2; Stefan Rieken3; Michael Ghadimi1; Tiago De Oliveira1;
Lena-Christin Conradi1
1Universitätsmedizin Göttingen, Klinik für Allgemein-, Viszeral- und
Kinderchirurgie, Göttingen, Deutschland
2Universitätsmedizin Göttingen, Institut für Medizinische Bioinformatik ,
Göttingen, Deutschland
3Universitätsmedizin Göttingen, Klinik für Strahlentherapie und Radioonkologie,
Göttingen, Deutschland
Background: Patients with rectal cancer in UICC stage II/III may
undergo neoadjuvant chemoradiotherapy (CRT). However, resistance
is a major clinically observed obstacle. Abnormal neoangiogenesis and
increased glucose metabolism are characteristics of cancer. In particular,
the bifunctional enzyme PFKFB3 represents a promising target. PFKFB3,
as an indirect stimulator of glycolysis, aects the glycolytic activity of
cancer cells and was shown to induce tumor vessel normalization upon
inhibiton. Moreover, high PFKFB3 expression was shown to be associated
with poor prognosis for patients with CRC. is highlights PFKFB3 as an
attractive therapeutic target.
Methods: We assessed the eect of PFKFB3 inhibition by 2E-3-(3-
pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) in CRC cell lines on
cell viability, cell death as well as invasion and migration ability. To verify
a potential radiosensitizing eect of 3PO a colony formation assay was
performed. Subsequently, in vivo studies were performed to evaluate the
TVN eect of combined therapy of 3PO and (C)RT in patient-derived
xenogras tumors.
Result: Our in vitro ndings showed that 3PO treatment of CRC cells
aects cell proliferation and viability in a concentration-dependent man-
ner and reduces CRC cell invasion and migration. In addition, we found
a radiosensitizing eect on CRC cells. Moreover, our results demonstrate
that inhibition of PFKFB3 induces TVN and alleviates tumor hypoxia
culminating in increased tumor necrosis upon combined therapy of 3PO
with (C)RT in vivo.
Discussion: Increased glycolysis and tumor hypoxia are thought to
induce resistance to radiotherapy in various tumors. We hypothesize that
RT resistance may be overcome by inducing TVN. A potential target is
PFKFB3, a crucial regulator of glycolysis. Here, we provide a rst insight
into the response of CRC cells to 3PO.
Conclusion: Finally, our in vitro and in vivo results support 3PO as a
potential future treatment complement for rectal cancer patients.
Disclosure Statement: e authors declare no conict of interest.
Poster
1
NOTCH Activation via gp130/STAT3 Signaling Confers
Resistance to Chemoradiotherapy
Melanie Spitzner1; Kristin Koerdel2; Thomas Meyer3; Niklas Engels2;
Florian Krause1; Jochen Gaedcke1; Lena-Christin Conradi1; Martin
Haubrock4; Tim Beißbarth5; Andreas Leha6; Steven A. Johnsen7;
B. Michael Ghadimi8; Stefan Rose-John9; Jürgen Wienands10;
Marian Grade8
1University Medical Center Goettingen, Department of General, Visceral and
Pediatric Surgery, Göttingen, Deutschland
2University Medical Center Goettingen, Institute of Cellular and Molecular
Immunology, Göttingen, Deutschland
3University Medical Center Goettingen, Department of Psychosomatic Medicine
and Psychotherapy, German Centre for Cardiovascular Research, Göttingen,
Deutschland
4University Medical Center Goettingen, Institute of Medical Bioinformatics,
Göttingen, Deutschland
5University Medical Center Goettingen, Institute of Medical Bioinformatics,
Goettingen, Deutschland
6University Medical Center Goettingen, Department of Medical Statistics,
Göttingen, Deutschland
7Mayo Clinic, Division of Gastroenterology and Hepatology, Gene Regulatory
Mechanisms and Molecular Epigenetics Laboratory, Rochester, USA
8University Medical Center Goettingen, Department of General, Visceral and
Pediatric Surgery, Goettingen, Deutschland
9Christian-Albrechts-University, Institute of Biochemistry, Kiel, Deutschland
10University Medical Center Goettingen, Institute of Cellular and Molecular
Immunology, Goettingen, Deutschland
Background: For locally advanced rectal cancer, the treatment concept
includes a preoperative chemoradiotherapy (CRT), followed by radical
surgical resection of the tumor. Unfortunately, the response to CRT varies
tremendously among patients, and about one third will have only little or
no response to the preoperative treatment. erefore, resistance of tumor
cells to CRT represents a fundamental problem in clinical oncology. e
underlying molecular mechanisms remain complex and have not yet been
suciently claried.
Methods: Blocking inammatory cytokine receptor signaling on response
to CRT was assessed in colorectal and esophageal cancer cell lines, com-
plemented by in vivo experiments using a rectal cancer xenogra mouse
model with fractionated CRT. Mutational analyses of STAT3 and studies
in the absence or presence of cytokine receptor activation were performed
to assess the requirement of active STAT3 signaling. To delineate how
inammatory signals control CRT resistance, global transcriptional activ-
ity was assessed using RNA sequencing.
Result: Here we show that blocking inammatory cytokine receptor
signaling via STAT3 re-sensitized treatment-refractory cancer cells and
abolished tumor growth in vivo when applied together with CRT. STAT3
executed treatment resistance by triggering the expression of RBPJ, the
key transcriptional regulator of the NOTCH pathway. e mandatory
RBPJ interaction partner, NOTCH intracellular domain, was provided
by tumor cell-intrinsic expression of NOTCH ligands that caused tonic
NOTCH proteolysis. In fact, NOTCH inhibition phenocopied the eect
of blocking STAT3 signaling. Moreover, genetic proling of rectal cancer
patients revealed the importance of the STAT3/NOTCH axis as NOTCH
expression correlated with clinical outcome.
Discussion and Conclusions: Our data uncovered an unprecedented
signal alliance between inammation and cellular development that
orchestrated resistance to CRT. Clinically, our ndings allow for biomark-
er-driven patient stratication and oer novel treatment options.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 63
103
Encorafenib and cetuximab in patients with metastatic,
BRAF V600E-mutated, colorectal carcinoma: a multi-centric,
multi-national, prospective, non-interventional study
inGermany, Austria and Switzerland – BERING CRC
Gerald Prager1; Gerdt Hübner2; Jan Schröder3; Helmut Forstbauer4;
Jens Kisro5; Manfred Welslau6; Dieter Bürkle7; Eyck von der Heyde8;
Harald Müller-Huesmann9; Beate Krammer-Steiner10; Christiane
Hering-Schubert11; Ulrich Popper12; Armin Gerger13; Richard Greil14;
Frank Reichenbach15; Dirk Arnold16; Ralph Fritsch17; Susanna Hegewisch-
Becker18; Arndt Vogel19; Anna Dorothea Wagner20; Thomas Winder21;
Dieter Koeberle22,23; Sebastian Stintzing24
1Department of Medicine I, Medical University Vienna, Vienna, Österreich
2oho - practice for oncology, Oldenburg i.H., Deutschland
3Oncological Practice Mülheim, Mülheim, Deutschland
4Practice Network Troisdorf, Troisdorf, Deutschland
5Oncological Practice Lübeck, Lübeck, Deutschland
6Oncological Practice Aschaenburg, Aschaenburg, Deutschland
7Oncological Practice Schorndorf, Schorndorf, Deutschland
8Oncological Practice Hannover, Hannover, Deutschland
9St. Josef Hospital Paderborn, Paderborn, Deutschland
10Department of Hematology and Oncology, Rostock South City Medical Center,
Rostock, Deutschland
11St. Georg Hospital Eisenach, Eisenach, Deutschland
12Department of Internal Medicine I for Hematology with Stem Cell
Transplantation, Hemostase-ology and Medical Oncology, Ordensklinikum Linz,
Linz, Österreich
13Division of Clinical Oncology, Medical University Graz, Graz, Österreich
14Paracelsus Medical University Salzburg, Salzburg Cancer Research Institute-
CCCIT and Cancer Cluster Salzburg, Salzburg, Österreich
15Pierre Fabre Pharma GmbH, Freiburg, Deutschland
16Asklepios Tumorzentrum Hamburg, AK Altona, Hamburg, Deutschland
17Klinik für Medizinische Onkologie und Hämatologie, Universitätsspital Zürich,
Zürich, Schweiz
18HOPE-Practice for Oncology Hamburg, Hamburg, Deutschland
19Hannover Medical School, Hannover, Deutschland
20Department of Oncology, Lausanne University Hospital and University of
Lausanne, Lausanne, Schweiz
21Internal Medicine II, Landeskrankenhaus Feldkirch, Feldkirch, Österreich
22Tumorzentrum, Claraspital Basel, Basel, Schweiz
23University Bern, Bern, Schweiz
24Department of Hematology, Oncology, and Cancer Immunology (CCM),
Charité - Universitaetsmedizin Berlin, Berlin, Deutschland
Background: Targeted treatment with encorafenib plus cetux-
imab represents a new standard of care for patients with BRAF
V600E-mutant metastatic colorectal cancer upon systemic therapy.
is combination has been approved in the EU and Switzerland in 2020.
e approval was based on the data from the BEACON CRC trial; the
updated analysis showed a median overall survival (mOS) of 9.3 months
for the treatment with encorafenib plus cetuximab compared to a mOS of
5.9 months with chemotherapy plus cetuximab (hazard ratio [HR], 0.61
[95% CI, 0.48 to 0.77]) and an objective response rate of 20% compared to
2%. e tolerability prole was consistent with the known safety prole.
As data from controlled clinical trials are based on a selected patient pop-
ulation, the non-interventional study (NIS) BERING CRC investigates
the use of encorafenib plus cetuximab under real-world conditions in a
broader patient population.
Methods: BERING CRC is an ongoing multi-national, multi-centric,
prospective, longitudinal NIS. It is the rst NIS to investigate the real-
world use of encorafenib plus cetuximab in BRAF V600E-mutant met-
astatic colorectal cancer upon systemic treatment in Germany, Austria
and Switzerland. e study aims to enroll 500 patients from 96 German,
Austrian and Swiss sites within an expected enrollment period of 6
yrs.e study observes patients treated according to the approval as given
in the respective Summary of Product Characteristics. e primary objec-
tive is to assess the 1-year OS rate. Secondary endpoints include ecacy,
quality of life, safety and tolerability of encorafenib plus cetuximab. e
inuence of prognostic factors on ecacy, as well as safety and tolerability
will also be assessed.
Result: From Sep 2020 to Apr 2022, 81 patients have been included from
80 open sites.
Discussion: Based on the initial 100 patients enrolled, a rst interim
analysis will be performed.
Conclusion: e study design and current enrollment status will be
presented.
Indication of source:
1 Koeberle D. et al., DGHO congress 2021, abstract #75
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organiser KUKM GmbH and KUKM
can disclose them if needed.
165
Forschungspartnerschaft Darmkrebs (Prioritiy Setting
Partnership Colorectal Cancer)– Identifying and prioritizing
unanswered questions about colorectal cancer
Magdalena Holze1; Rosa Klotz1; Colette Dörr-Harim2; Azaz Ahmed3;
André Mihaljevic2
1Chirurgische Klinik, Heidelberg, Deutschland
2Uniklinik Ulm Abt Chirurgie, Ulm, Deutschland
3Nationales Centrum fu¨r TumorerkrankungenNCT, Heidelberg, Deutschland
Background: Colorectal cancer (CRC) is the third most common can-
cer worldwide and the second and third leading cause of cancer death
in women and men. With improving therapeutic options, the number of
elderly people living with CRC increases.
Research projects are currently driven by scientists or pharmaceuti-
cal industry whereas other stakeholders like patients, carers, physi-
cians etc. are rarely involved. Accordingly, it remains unclear which
research questions should be answered with high priority. To address
this mismatch, the “Priority Setting Partnership Colorectal Cancer”
(Forschungspartnerscha Darmkrebs (FP)) was initiated. e FP brings
patients, carers, clinicians and other relevant stakeholders together to
identify and prioritize the most important unanswered questions about
diagnostics, therapy and oncological aercare of CRC with an emphasis
on special needs of elderly patients.
Methods: Supported by the UK-based James Lind Alliance the FP is per-
formed by the following method ensuring transparency of the process and
balanced inclusion of all stakeholders’ interests and perspectives. Aer
creating a Steering Group, 1108 questions were gathered via a nationwide
survey. Responses were summarized, categorized and a systematic litera-
ture search was performed to check against current evidence. In a second
survey, interim priority setting was carried out. In September 2021, in the
nal consensus workshop the TOP 10 list of research priorities will be
identied which will be published and promoted to initiate relevant future
projects.
Result: At the congress the nal results of the TOP 10 list will be presented.
Discussion: Priorities identied in the FP CRC provide an important
basis for future research to initiate patient-centered research and funding.
Conclusion: e introduced FP is the rst nationwide project with this
new approach of patient involvement bringing together all stakeholders in
CRC in prioritizing future research.
Disclosure Statement: e authors declare no conict of interest.
170
Methylated septin 9 as a progression parameter in colorectal
cancer compared to CEA and CA19-9
Laura Schulz1; Sabine Leerho1; Ernst W. Kolbe1; Arnold M. Raem1;
Günther Winde1
1Medizin Campus Ostwestfalen der RUB, Klinikum Herford, Universitätsklinik
für Allgemein- und Viszeralchirurgie, Thoraxchirurgie und Proktologie, Herford,
Deutschland
Purpose: To improve the prognosis of patients suering from colorectal
cancer, reliable follow-up is crucial. So far, CEA and CA19-9 are used for
routine monitoring, despite their limited sensitivity. erefore, detecting
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts64
circulating tumour cells or tumour DNA in plasma could be of greater
value, e.g. the use of “methylated Septin 9” for “liquid biopsy”. In this
study mSEPT9 was investigated as a possible progression parameter in
colorectal cancer and compared to the common tumour markers.
Methods: DKG-accredited (ST-D469), prospective single center study,
n = 122, m/f patients from Herford University Dept. of Surgery with col-
orectal cancer UICC stage I-IV, curative intention to treat. Blood sam-
pling: preoperatively and postoperatively at 1/ 6/ 12 weeks tested for
mSEPT9, CEA and CA19-9 using Epi-proColon® 2.0 test and ECLIA.
e results have been validated by the relative amount of extracted DNA
(ACTB), the use of control samples and by reaching the dened crossing
point value (CP) < 40.5 for all PCR control replicates. 2/3 positiv PCR
replicates indicated a Septin9-positive result. Results were analysed using
GraphPad Prism™.
Results: Preoperatively, mSEPT9 appeared more sensitive (52%) than
CEA (31%) and CA19-9 (14%). 3 months postoperatively, the patholog-
ical test results reduced for mSEPT9 (25%) and CEA (23%), but not for
CA19-9 20%. e highest sensitivity was achieved by mSEPT9 in stage
UICC IV (94%) and T4 (87%) or tumour localisation in the colon (53%;
rectum 51%). mSEPT9 indicated metastases (sensitivity 83%) and resid-
ual tumour (R1: 50%; R2:100%).
Discussion: So far, mSeptin 9 has only been investigated as a screening
parameter. Studies from Devos et al. (2009) and Ørnto et al. (2015)
demonstrated the high specicity (82-95%) and a low false positive rate of
the Epi-proColon® 2.0 CE test (4-5%).
Conclusion: Our results show the benecial use of mSeptin9 as a potent
follow-up parameter of colorectal cancer especially for R+ status patients.
A prospective comparison of the R+ patients with PET-CT-results is
planned.
Disclosure Statement: e authors declare no conict of interest.
245
RAS mutant metastatic colorectal cancer – Real-world data
from more than 1000 patients from the Clinical Tumor
Registry Colorectal Cancer (TKK)
Steen Dörfel1; Christiane Bernhardt2; Egbert Eggers3; Stefan Fruehauf4;
Christoph Maintz5; Joachim Behringer6; Anna Hof7; Natalie Wetzel7;
Lisa Kruggel7; Karin Pottho7
1Onkozentrum Dresden/Freiberg, Dresden, Deutschland
2Gemeinschaftspraxis für Hämatologie und Onkologie, Dortmund, Deutschland
3Kreiskrankenhaus Torgau Innere Medizin Darmzentrum, Torgau, Deutschland
4Klinik Dr. Hancken Hämatologie und Onkologie, Stade, Deutschland
5MVZ West GmbH Würselen Hämatologie-Onkologie, Würselen, Deutschland
6Onkologische Schwerpunktpraxis Speyer, Speyer, Deutschland
7iOMEDICO, Freiburg, Deutschland
Background: For patients (pts) with RAS mutant (mut) metastatic col-
orectal cancer (mCRC) the therapeutic benet derived from established
treatment regimens is still unclear. Guidelines recommend chemotherapy
(CT; uoropyrimidine, irinotecan, oxaliplatin) with/without anti-angio-
genic agents for two treatment lines. ere is no established standard of
care for subsequent treatment lines. Real-world data on pts with RAS mut
mCRC are scarce.
Methods: Since 2006, the Tumor Registry Colorectal Cancer (TKK) pro-
spectively collects data on patient and tumor characteristics, treatment,
outcome, and quality of life of CRC pts in routine practice in Germany.
e treating physicians decide treatments as per clinical routine and inde-
pendently from the registry. Here we analyze patient and tumor charac-
teristics, longitudinal treatment details and outcome of 1087 pts with (K)
RAS mut mCRC from begin of palliative rst-line therapy.
Result: Between 2010 and 2018, 1087 pts with (K)RAS mut mCRC were
enrolled. Median age of pts was 68 years. Since 2010, KRAS testing could
be documented. Since 2014 details on extended RAS mutation status test-
ing (exons 2/3/4 for KRAS or NRAS) were documented (n=897).
Pts with (K)RAS mut mCRC were mostly treated with FOLFIRI+BEV
(30%), FOLFOX+BEV (25%), FOLFOX (13%) and FOLFIRI (9%).
No major changes were seen in choice of treatment over time. 747 pts
(69%) received 2nd-line therapy, of those 18% of pts were treated with
FOLFIRI+BEV followed by FOLFOX+BEV (16%). 439 pts (40%) received
3rd-line therapy, of those 12% of pts received FOLFIRI+BEV. e percent-
age of pts receiving 3rd-line triuridine/tipiracil increased from 9% in
2016 to 38% in 2019.
Median overall survival for all evaluable pts with (K)RAS mut mCRC was
21.9 months (62% events, 95%-CI: 20.9 - 23.0 months). Updated data will
be presented.
Conclusion: is analysis of the RAS mut mCRC population enrolled
prospectively in the TKK database provides important insights into treat-
ment patterns, sequential treatments, and outcome of patients with RAS
mut mCRC in routine clinical practice in Germany.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organiser KUKM GmbH and KUKM
can disclose them if needed.
276
Survival of patients (pts) with BRAF V600E mutated metastatic
colorectal cancer (mCRC) treated with systemic therapy in a
real-world setting
Moritz Götz1,2,3; Stefan Kasper2,3,4; Andreas Paul2,3,5; Peter Markus6;
Brigitte Schumacher7; David Albers7; Vivian Rosery2,4; Katharina Laue2,4;
Gregor Zaun2,4; Karina Kostbade2,4; Michael Pogorzelski2,4;
Kurt Werner Schmid1,2,3; Hans-Ulrich Schildhaus1,2,3; Marcel Wiesweg2,3,4;
Martin Schuler2,3,4; Isabel Virchow2,4
1West German Cancer Center, University Hospital Essen, Institute of Pathology,
Essen, Deutschland
2Medical Faculty University Duisburg-Essen, Essen, Deutschland
3German Cancer Consortium (DKTK), Partner site University Hospital Essen,
Essen, Deutschland
4West German Cancer Center, University Hospital Essen, Department of Medical
Oncology, Essen, Deutschland
5West German Cancer Center, University Hospital Essen, Department of General,
Visceral and Transplant Surgery, Essen, Deutschland
6Elisabeth Hospital Essen, Department of General Surgery and Traumatology,
Essen, Deutschland
7Elisabeth Hospital Essen, Department of Gastroenterology, Essen, Deutschland
Background: Pts with BRAF mutated mCRC have a dismal prognosis
with median overall survival (OS) times of only 1.5 years in clinical trials.
Current guidelines recommend intensive 1st-line chemotherapy (CTX)
with FOLFOXIRI, and 2nd line with a BRAF inhibitor (BRAFi) in combi-
nation with EGFR antibodies. However, in real-world, a substantial num-
ber of pts do not qualify for intensive CTX. e best therapeutic strategies
in these pts remain elusive. Here, we present data from BRAF mutated
mCRC pts treated at a large German comprehensive cancer centre.
Methods: is is a retrospective single-center analysis. Clinico-
pathological data and treatments were extracted from the electronical
health record. Progression free-survival (PFS) was dened from start of
CTX to progress or death, OS was dened from start of palliative CTX
until death, pts were censored at time point of last follow up. Type of CTX
was correlated with PFS and OS.
Result: In total, 51 evaluable pts were identied. Median age was 62.2
years, and 58.9% were female. In 71.4% of pts, primary tumour was right-
sided, and 26.1% had a dMMR status. Palliative CTX was administered
to 48 pts, while 3 pts only received BSC. Pts received 2 treatment lines in
median (range 0-5). FOLFOXIRI was administered to 12 pts (23.5%), 19
pts received FOLFOX/CAPOX, and 10 pts received FOLFIRI. A monoclo-
nal antibody (moABX) was added in 31 pts, mainly bevacizumab. Median
PFS was 8.4 months (mo) and median OS was 17.6 mo. Interestingly,
FOLFOXIRI was associated with a signicant prolonged PFS (HR 0.325;
p=0.026) but had no signicant impact on OS (HR 0.742: p=0.433). In
contrast, the use of moABX in 1st-line was associated with prolonged OS
(HR 0.523; p=0.043). In further lines, 17 pts received a BRAFi. ese pts
had a numerical longer OS of 25.1 mo compared to pts without BRAFi
therapy (13.1 mo).
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 65
Conclusion: In a real-world setting, comparable survival times could be
achieved in pts with BRAF mutated mCRC as in recently published trials.
Intensive 1st-line therapy has no impact on OS. e implementation of
moABX and BRAFi during therapy correlates with prolonged OS.
Disclosure Statement: e authors declare the following: Merck, Amgen, Roche,
Sano, Aventis, Servier, Lilly
311
Epidemiology and prognostic risk factors of appendiceal
neoplasia histological subtypes
Kathrin Halfter; Anne Schlesinger-Raab; Gabriele Schubert-Fritschle;
Jutta Engel
Institute for Medical Information Processing, Biometry and Epidemiology (IBE),
Ludwig-Maximilians-University (LMU), Munich Cancer Registry (MCR), München,
Deutschland
Purpose: Appendiceal neoplasia are a rare subtype of colorectal tumors,
the few available studies are mostly based on SEER data and lack infor-
mation on mucinous neoplasia. e aim of this retrospective registry
study was to assess epidemiology and prognosis in a European popula-
tion-based cohort of eected patients.
Methods: e nal analyses included 1 097 patients from the Munich
Cancer Registry (MCR) diagnosed between 1998 and 2020. Cases were
grouped according to tumor histology into adenocarcinoma (ADENO),
neuroendocrine neoplasia (NEN), mixed adeno-neuroendocrine car-
cinoma (MANEC), and mucinous neoplasia (LAMN and HAMN).
Joinpoint trend analysis and baseline demographic comparisons were
conducted, in addition to survival analyses using competing risk and uni-
variate/multivariate methods.
Result: Until 2016 the number of cases increased signicantly (APC =
6.86, p < .001) followed by a decline in the following years (APC = -14.82,
p = .014; average APC = 2.5, p = .046).
In univariate analysis patients with NEN (48.4%) and mucinous neo-
plasms (11.6%) fared compariably better than ADENO (36.0%) and
MANEC (3.0%, p < .0001).
A multivariate analysis revealed further histological classication was not
prognostically relevant, while older age and UICC III/IV at diagnosis were
associated with a lower prognosis. In the ADENO subgroup a high tumor
grading and a less extensive surgical tumor resection procedure were also
associated with poorer survival.
Conclusion: e previously observed increase in cases appears to be
abating, potentially due to fewer appendicitis and/or appendectomies.
Appendiceal neoplasia are histologically heterogeneous, however this
diversity becomes less relevant compared to the marked dierence to can-
cers of the remaining colon.
Disclosure Statement: e authors declare no conict of interest.
345
Case of a patient with response to combined immune
checkpoint inhibition after progression on pembrolizumab
Carolin Krekeler1; Georg Evers1; Kerstin Menck1; Andrea Kerkho1;
Wolfgang Hartmann2; Andreas Pascher3; Georg Lenz1; Micha Peeck1,4;
Annalen Bleckmann1,4
1Dept. of Medicine A - Hematology, Hemostaseology, Oncology and
Pneumology , University Hospital Münster, Münster, Deutschland
2Dept. of Pathology, University Hospital Münster, Münster , Deutschland
3Dept. of General, Visceral and Transplant Surgery, University Hospital Münster,
Münster, Deutschland
4Authors contributed equally
Background: Metastatic colorectal cancer (mCRC) with high frequency
of microsatellite instability (MSI-H) responds poorly to cytotoxic ther-
apy. e underlying mismatch repair deciency leads to the creation of
neoantigens and thus immunogenic epitopes. Treatment with immune
checkpoint inhibitors (ICI) shows ecacy and long-term response in a
proportion of mCRC patients. Single-agent ICI is the current standard of
care. Nevertheless, some patients with initial response to single-agent ICI
eventually develop progressive disease. ere are no generally accepted
recommendations regarding treatment in this situation.
Methods: We present a scientic report on the clinical course of a patient
with MSI-H mCRC treated with the combination of nivolumab (3 mg/kg)
and ipilimumab (1 mg/kg) every 3 weeks aer image-conrmed progres-
sion on pembrolizumab.
Result: A 64-year old male patient with hepatic, bone, port site and sub-
cutaneous metastases received nivolumab and ipilimumab aer tumor
progression on pembrolizumab. Aer two cycles a clinical response with
a shrinkage of the palpable subcutaneous metastases was observed. Aer
three cycles of combined ICI therapy, PET-CT revealed a partial response
with a complete metabolic remission of the bone lesion and regression
of all other metastases. Moreover, CEA and CA 19-9 levels declined and
normalized while the clinical performance status improved. e patient
tolerated the treatment well, except for pain one week aer the application
of ICI, which was controlled by oral opioids. Aer 4 cycles of combined
ICI the patient is continuing single-agent nivolumab.
Discussion: ICI are able to provide durable responses in MSI-H mCRC.
erefore, testing for MSI is required. In the case of progression on sin-
gle agent anti-PD-1 blockade, the addition of an anti-CTLA-4 drug might
help to overcome an acquired resistance to ICI monotherapy.
Conclusion: Further clinical trials are needed in order to verify the e-
cacy and safety of combined immunotherapy aer progression on single
agent ICI.
Disclosure Statement: e authors declare no conict of interest.
379
Colorectal cancer risk: the interplay of polygenic risk,
high-impact monogenic variants, and family history
Emadeldin Hassanin1; Dheeraj Bobbili2; Rana Aldisi1; Friederike David3;
Hannah Klinkhammer1,4; Nuria Dueñas5,6; Andreas Mayr4; Markus
Nöthen3; Robert Hüneburg7,8; Andreas Forstner3,9,10; Isabel Spier3,8;
Patrick May2; Peter Krawitz1; Carlo Maj1; Stefan Aretz3,8
1Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn,
Bonn, Deutschland
2Luxembourg Centre for Systems Biomedicine, University of Luxembourg,
Esch-sur-Alzette, Luxemburg
3Institute of Human Genetics, Medical Faculty, University of Bonn, Bonn,
Deutschland
4Institute for Medical Biometry, Informatics and Epidemiology, Medical Faculty,
University Bonn, Bonn, Deutschland
5Catalan Institute of Oncology-IDIBELL, ONCOBELL, Hospitalet de Llobregat,
Barcelona, Spanien
6Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto
Salud Carlos III, Madrid, Spanien
7Department of Internal Medicine I, University Hospital Bonn, Bonn,
Deutschland
8National Center for Hereditary Tumor Syndromes, University Hospital Bonn,
Bonn, Deutschland
9Centre for Human Genetics, University of Marburg, Marburg, Deutschland
10Institute of Neuroscience and Medicine (INM-1), Research Center Ju¨lich, Jülich,
Deutschland
Background: Common, low penetrant genetic risk variants (SNPs) asso-
ciated with colorectal cancer (CRC) are distributed in the population.
Summarised in quantitative polygenic risk scores (PRS), the combined
eect might explain a substantial fraction of CRC risk variability and can
identify individuals at several times lower and greater CRC risk than the
general population. e study aims to investigate to which extent PRS,
high-impact monogenic variants for hereditary CRC (Lynch syndrome,
polyposis), and family history aect CRC risk by assessing cancer prev-
alence and cancer cumulative lifetime incidence using European popula-
tion-based data.
Methods: 163,516 individuals from the UK Biobank were stratied as fol-
lows: 1. carriers or non-carriers of rare, pathogenic germline variants in
CRC susceptibility genes, 2. individuals with low (<10%), intermediate
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts66
(10-90%) or high (>90%) PRS, and 3. individuals with or without a fam-
ily history of CRC. Multivariable logistic regression was used to compare
the odds ratio (OR) across the dierent groups while Cox proportional
hazards models were used to compute the cumulative lifetime incidence.
Result: Taking non-carriers with intermediate PRS as reference, CRC
cumulative lifetime incidence by age 78 years for carriers of monogenic
variants with low PRS is 22% and reaches 66% for carriers with high PRS,
compared to 7% and 31% for non-carriers, respectively. A suspicious fam-
ily history is associated with a further increase of the cumulative incidence
reaching 75% for carriers and 35% for non-carriers.
Discussion: e ndings demonstrate that CRC risk is strongly inu-
enced by the PRS for both a sporadic and hereditary background. A high
PRS in non-carriers confers a CRC risk comparable to monogenic vari-
ants. Family history, monogenic variants, and PRS contribute additively
to CRC risk.
Conclusion: e implementation of PRS in routine patient care will likely
improve individualised risk stratication for sporadic and hereditary
CRC, which will in turn guide tailored preventive strategies in high, mod-
erate, and low risk groups.
Disclosure Statement: e authors declare no conict of interest.
515
Eectiveness of care in German cancer centres – evidence
from the WiZen study
Veronika Bierbaum1; Martin Rößler1; Bobeth Christoph1; Michael Gerken2;
Kees Kleihues-van Tol2; Patrik Dröge3; Andreas Kloess3; Christian Günster3;
Monika Klinkhammer-Schalke2,4; Olaf Schoer1; Jochen Schmitt1
1Universitätsklinikum Carl Gustav Carus Dresden, Zentrum für Evidenzbasierte
Gesundheitsversorgung (ZEGV), Dresden, Deutschland
2Tumorzentrum Regensburg, Regensburg, Deutschland
3Wissenschaftlichs Institut der AOK (WIdO), Berlin, Deutschland
4Arbeitsgemeinschaft Deutscher Tumorzentren e.V., Berlin, Deutschland
Background: Treatment of cancer patients in certied cancer centers is
a national health care goal in Germany. While previous studies provide
some evidence that treatment in cancer centers certied by the German
Cancer Society (GCS) is associated with better patient outcomes, there
is a lack of comprehensive analysis across large populations. e study
“Eectiveness of care in German cancer centres” (WiZen) aims to close
this gap.
Methods: WiZen is a retrospective cohort study covering patients with
eight types of incident cancer in the period 2007-2017. e study is
based on nationwide health insurance data provided by WIdO (the AOK
research institute) and data from clinical cancer registries. Here, we report
results for patients with colon cancer (CC)/rectal cancer (RC) (ICD-
10-GM: C18-C20), and pancreatic cancer (PC) (ICD-10-GM: C25) based
on health insurance data. We estimated dierences in survival between
patients treated in GCS-certied cancer centers and non-certied hospi-
tals using relative survival analysis and applied Cox regression with shared
frailty to adjust for multiple patient (demographics, comorbidities and
indicators of tumor stage) and hospital characteristics.
Result: 109,518 patients with CC, 51,417 patients with RC, and 45,318
patients with PC were included. In line with relative survival analysis,
hazard ratios (HRs) derived from Cox regressions adjusting for potential
confounders on both the patient and the hospital level indicated a signi-
cantly lower hazard of death in patients treated in GCS-certied cancer
centers across all three cancer types (CC: HR=0.92, 95%-CI=0.89-0.95;
RC: HR=0.92, 95%-CI=0.88-0.95; PC: HR=0.89; 95%-CI=0.85-0.93).
Discussion: Drawing on a large sample and adjusting for multiple poten-
tial confounders, our ndings provide evidence that treatment in GCS-
certied cancer centers is related to better survival in patients with CC,
RC, and PC.
Conclusion: is observational evidence strongly suggests that certi-
cation of hospitals is a powerful means to improve patient outcomes in
cancer care.
Disclosure Statement: e authors declare no conict of interest.
535
Patient-individual tumor-derived models from CRC patients
and their potential in therapy prediction for CRC metastases
Christina Mullins; Sandra Wagner; Randy Przybylla; Florian Bürtin;
Michael Linnebacher
Universitätsmedizin Rostock, Allgemein-, Viszeral-, Thorax-, Gefäß- und
Transplantationschirurgie, Rostock, Deutschland
Background: Metastatic colorectal cancer (CRC) is a threatening diag-
nosis as overall survival is still very low. erefore, patients and physi-
cians are in need of better therapeutical options and enhanced therapy
response predictions. Our aim was to investigate the predictive capacity
of primary CRC tumor material for treatment responses of corresponding
metastases.
Methods: First, the mutational landscape of primary tumors and corre-
sponding metastases of 10 CRC patients was compared. Next, we investi-
gated cell line pairs of primaries and metastases for four of those patients
with regard to cell line characteristics and drug sensitivity. Finally, in a
proof of concept approach, PDX models of on patient were treated in vivo.
Result: Driver mutations did not dier between primaries and metasta-
ses but the latter tended to further accumulate mutations, many of still
uncertain signicance. In vitro chemosensitivity testing did not reveal
notable dierences in response to 5-FU and oxaliplatin between tumor
and corresponding metastasis cell lines. However, response to irinotecan
diered: the majority of investigated metastases-derived cell lines was less
sensitive to irinotecan than their primary tumor-derived cell line counter-
part. erapy recommendations based on these ndings were compared
with clinical treatment response and were oen in line with the predicted
therapy outcome.
Discussion: Primary tumor cell models seem to be a good tool to test
drug responses and draw conclusions for (potential) future metastases.
Conclusion: With an increasing number of data from tumor-derived cell
lines, such predictions could improve clinical treatment decisions, both
recommending likely most eective therapeutic options while excluding
ineective treatments and thus saving patients from side eects and early
development of resistant tumor cell clones.
Disclosure Statement: e authors declare no conict of interest.
539
Rectal Cancer and Risk of Secondary Cancer:
A Population-Based Study
Anne Schlesinger-Raab; Kathrin Halfter; Gabriele Schubert-Fritschle;
Jutta Engel
Tumorregister München (TRM) am Institut für Medizinische
Informationsverarbeitung Biometrie und Epidemiologie (IBE),
Ludwig-Maximilians-Universität München (LMU), München, Deutschland
Background: To investigate the risk of secondary cancer and therapy-in-
duced secondary primary cancer (SC) following primary rectal cancer
therapy.
Methods: All analyses were calculated on the basis of a population-based
cohort of rectal cancer patients diagnosed between 1998 and 2019 within
the catchment area of the Munich Cancer Registry (MCR). Cumulative
incidence (CI) with competing risks, survival analyses (overall (OS) and
relative (RS) survival), and multiple regression analyses (Fine-Gray)
were used to compare time periods (1998-2005, 2006-2013, 2014-2019),
sex and treatment. Analyses were similarly done on a propensity score
matched cohort.
Result: A total of 13,919 invasive primary M0 rectal cancer cases with
tumour resection were included. Median age of patients with or without
radiotherapy (RTX) diered between 65.0 yrs. and 70.3 yrs. In UICC
stage I, II and III, RTX was conducted in 10.7%, 48.9% and 59.3%, respec-
tively. 11,687 single rst M0 tumours were analysed for OS, RS and CI
of SC. 5-year OS/ RS improved from 69%/ 80% in the rst time period
to 74%/85% in the last. e 5-yr. CI of any SC was 6.1% in the rst time
period and decreased subsequently: in 2006-2013 the 5-yr. CI was 4.9%,
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 67
in 2014-2019 it was 4.0% (p<.0001). Sex dierences in 5-, 10- and 20-yr.
CI were distinct: 5.5%, 10.9% 18.5% in male, 4.6%, 8.8%, 14.9% in female
(p<.0001). Fine-Gray regression modelling of CI of SC found a small sig-
nicant eect of chemotherapy (CTX) increasing the risk of SC in total,
HR 1.22 (1.03-1.45) but no signicant eect of RTX. In men, a signicant
eect of RTX was found decreasing the risk of SC in the prostate, HR 0.46
(0.29-0.73). is eect for men was as well found in the PSM cohort.
Discussion: Although regression models were adjusted for age and
tumour characteristics, RTX in rectal cancer decreases the risk of prostate
cancer as a SC. e eect is also found in the analysed PSM cohort. A
plausible explanation is missing.
Conclusion: ere was no strong evidence for therapy-induced SC in rec-
tal cancer patients.
Disclosure Statement: e authors declare no conict of interest.
627
Plant polyphenols unexpectedly aggravate colon cancer liver
metastases via enhanced inammation
Johanna Roth1; Laura Robrahn1; Merve Erdem1; Athanassios Fragoulis2;
Ulf Peter Neumann1; Thorsten Cramer1
1Klinik für Allgemein-, Viszeral und Transplantationsmedizin, Uniklinik RWTH
Aachen, Aachen, Deutschland
2Institut für Anatomie, Uniklinik RWTH Aachen, Aachen, Deutschland
Purpose: Epidemiological data show reduced cancer incidence and
mortality in vegetarians. e benecial eect is thought to be mediated
partly by plant phytochemicals (PP). While a wealth of data show tumor-
inhibiting eects of PP in vitro and in immunodecient rodent models,
the consequences of these substances on tumor growth in mice with a
functioning immune system remain largely elusive.
Methods: Immunocompetent C57Bl6/J mice harboring liver metastases
(murine colon cancer cell line MC38) were gavaged once daily for 10 days
with a vegetable extract (VE) from garlic, beetroot, broccoli, Brussels
sprouts, cauliower, spinach and curcuma supplied with Epigallocatechin-
gallate from green tea. Tumors were counted and analyzed via immuno-
histochemistry (IHC).
Results: In vitro treatment of MC38 cells with the VE resulted in a
dose-dependent inhibition of proliferation and, ultimately, cell death.
Against this background we were intrigued to note that metastatic nod-
ules in the VE-treated mice were signicantly larger compared to water-
treated controls. IHC demonstrated signicant greater abundance of
leukocytes (CD45) and F4/80+ macrophages around the metastases in
the VE group. To address the functional importance of this nding, we
combined the VE with a an anti-inammatory agent (prednisolone). is
resulted in signicantly smaller metastases, supporting the idea that the
VE aggravates tumor formation via inammation.
Discussion: Our results conrm published data as they show anti- tumor
eects of PP in vitro. e unexpected nding of aggravated metastatic
growth in vivo upon oral supplementation with PP might be partly
explained by higher abundance of tumor-supporting leukocytes.
Conclusion: Our results once again demonstrate that results from cell cul-
ture studies and immunodecient rodent models have to be validated in
properly functioning animal models. e eects of PP on the immune sys-
tem are to be taken seriously and warrant further and thorough analysis.
Disclosure Statement: e authors declare no conict of interest.
718
Recapitulating Drug Treatment in a Dish - Investigating the
Impact of 2D Versus 3D In Vitro Cancer Models and Dierent
Treatment Schemes on Drug Response
Sushmitha Sankarasubramanian1,2; Anne-Claire Kröger3; Ulrike Pfohl1;
Jürgen Loskutov1; Michael Linnebacher4; Christian Regenbrecht1,5,6;
Lena Wedeken1
1CELLphenomics GmbH, Berlin, Deutschland
2Chirurgische Klinik, Universitätsklinikum Erlangen, Department of Surgery,
Erlangen, Deutschland
3Ruprecht-Karls-Universität Heidelberg , Fakultät für Biowissenschaften,
Heidelberg, Deutschland
4Universitätsmedizin Rostock, Chirurgische Klinik und Poliklinik, Molekulare
Onkologie und Immuntherapie, Rostock, Deutschland
5ASC Oncology GmbH, Berlin, Deutschland
6Universitätsklinikum Göttingen, Institut für Pathologie, Göttingen, Deutschland
Background: Cancer is a heterogenous disease and understanding the
disease biology and developing eective therapeutics benets greatly from
the use of suitable in vitro cell culture models. Established 2D lines have
been used as a base for discovery and proof of concept studies for the past
50 years (1, 2). In recent years, patient-derived 3D tumor models emerged
as a powerful tool to address cancer biology and assess drug sensitivity
(3, 4).
Methods: 2D colon cancer cell lines and thereof derived 3D colon cancer
models were treated with standard-of-care chemotherapeutics as well as
targeted therapies following the same protocol. In addition, for therapeu-
tic compounds given daily in clinic the eect of single vs daily dosing on
cancer cell drug sensitivity was evaluated. Cell viability measurement was
used to assess drug response.
Result: Drug response diered between cancer cell models cultured in 2D
and 3D, as well as between single and daily treatment schedules.
Discussion: Even though the use of 2D cell lines for testing of chemother-
apeutics and basic research is indisputable, patient-derived in vitro 3D
cancer models better recapitulate the cancer histology, genetic set up and
heterogeneity. In addition, drug sensitivity is inuenced by 2D versus 3D
culture conditions further questioning the use of 2D cell lines to mimic
tumor phenotype and functional activity.
Conclusion: e type of in vitro cancer model and drug treatment sched-
ule impact drug response. erefore, the selection of an appropriate
model and treatment scheme are crucial to derive data that can be used
for clinical decision making.
Indication of source
1. B. P. Lucey, W. A. Nelson-Rees, G. M. Hutchins, Arch Pathol Lab Med. 133,
1463–1467 (2009).
2. J.-P. Gillet, S. Varma, M. M. Gottesman, Jnci J National Cancer Inst. 105,
452–458 (2013).
3. M. Schütte et al., Nat Commun. 8, 14262 (2017).
4. G. Vlachogiannis et al., Science. 359, 920–926 (2018).
Disclosure Statement: e authors declare the following: Christian Regenbrecht
is shareholder at CELLphenomics GmbH, a company oering drug screens on or-
ganoid models, and ASC Oncology GmbH, a company involved in patient specic
therapy prediction.
726
Remarkable tumor response after addition of epidermal
growth factor receptor monoclonal antibody therapy
combined with irinotecan based chemotherapy in patient
with primary chemotherapy resistant metastatic colorectal
cancer with KRAS G13D mutation – A case report
Judith Gold; Jorge Riera Knorrenschild; Andreas Neubauer
Marburg, UKGM Marburg , Hämatologie/Onkologie, Marburg, Deutschland
Background: Additional treatment with EGFR antibody therapy can lead
to partial tumor regression in initially chemotherapy-resistant mCRC
with KRAS G13D mutation.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts68
Methods: A 30-year-old female presented with ileus. Emergency right
hemicolectomy followed showing an adenocarcinoma of coecum. MSS.
No BRAF- or NRAS-, but KRAS G13D mutation. Staging showed multi-
ple liver but no further metastases (UICC IVa).
Result: e liver metastases were considered non-resectable in local
tumorboard. We applied an aggressive chemotherapy regime (5 courses
FOLFOXIRI + Bevacizumab). 2 month later liver metastases were pro-
gressive. In primary chemotherapy-resistant tumor it is not expected that
2nd line therapy can lead to sucient response. Cetuximab is an EGFR
antibody which is ocially not approved for treatment KRAS mutated
mCRC because most studies predicted potential disadvantage to survival.
Discussion: Some studies suggested that KRAS G13D mutated tumors
may benet from cetuximab application combined with chemother-
apy better than tumors with other KRAS mutations 1²³. Regarding this,
Cetuximab was added while proceeding with FOLFOXIRI. Aer 6 courses
of FOLFOXIRI with Cetuximab instead of Bevacizumab staging showed
regressive metastases. PET-CT still showed active metabolism. Metastatis
were now considered resectable. Chemotherapy was continued due to ser-
vere side eects without Oxaliplatin and Irinotecan. Aer altogether 11
courses staging showed progressive disease, just before surgery could be
conducted. Aer no response to Lonsurf + Bevacizumab the patient died
12 month aer diagnosis.
Conclusion: It seems remarkable that in primary chemotherapy-resistant
mCRC with KRAS G13D mutation simply by switching antibody therapy,
tumor response could be achieved. Switching antibody therapy may be
considered for 2nd line treatment.
Indication of source:
1 Chen J et al. DOI: 10.1007/s00280-012-2005-9; 2 Mao et al. DOI: 10.1002/
cncr.27804; 3 McFall et al. DOI: 10.1126/scisignal.aaw8288
Disclosure Statement: e authors declare no conict of interest.
736
T stage-dependent lymph nodes (LN) and distant metastases
as well as accuracy of LN assessment in rectal cancer
Henry Ptok1; Frank Meyer2; Roland S. Croner2; Ingo Gastinger3;
Benjamin Garlipp3
1Dept. of General and Abdominal Surgery, Municipal Hospital (“Ernst-von-
Bergman-Klinikum”), Potsdam, Deutschland
2Dept. of General, Abdominal, Vascular and Transplant Surgery, Otto-von-
Guericke University at Magdeburg with University Hospital, Magdeburg,
Deutschland
3Intitute of Quality Assurance in Operative Medicine, Otto-von-Guericke
University at Magdeburg, Magdeburg, Deutschland
Background: Up to now, investigation of a high number of lymph nodes
in rectal cancer was considered the basis of an accurate staging. However,
recently published data indicate that despite improved diagnostic of
lymph nodes no tumor stage migration can be found. In this context, the
authors have substantial doubt with regard to the “upstaging hypothesis”.
Aim: To analyze data obtained in a representative number of patients with
primary rectal cancer with regard to lymph node diagnostic and related
tumor stages.
Methods: In pT2-, pT3- and pT4 rectal cancer lesions, the impact of
investigated lymph nodes onto the frequency of pN+ status, the cumula-
tive risk of metachronous distant metastases as well as overall survival was
studied by means of a prospective multicenter observational study over a
dened period of time.
Results: From 2000-2011, the portion of surgical specimens with ≥ 12
investigated lymph nodes increased signicantly from 73.6 % to 93.2 %
(p<0.001) and the number of investigated lymph nodes from 16.2 onto
20.8 (p<0.001). Despite this, the percentage of pN+ rectal cancer lesions
varied only non-signicantly (39.9 % to 45.9 %; p=0.130; median, 44.1 %).
For pT2, pT3 and pT4 rectal cancer lesions, there was an increasing por-
tion of pN+ ndings correlating signicantly with the number of inves-
tigated lymph nodes up to n=12 investigated lymph nodes. Only in pT3
rectal cancer, there was a signicant increase of pN+ ndings in case of
> 12 lymph nodes (p=0.001) but not in pT2 (p=0.655) and pT4 cancer
lesions (p=0.256). For pT3 pN0 cM0 rectal cancer, risk of metachronous
distant metastases and overall survival did not depend on the number of
investigated lymph nodes.
Conclusion: In rectal cancer, at least n=12 lymph nodes are to be min-
imally investigated. e investigation of less lymph nodes is associated
with a higher risk of false-negative pN0 ndings. In particular, in pT3 rec-
tal cancer the investigation of more than 12 lymph nodes lowers the risk of
false-negative pN0 ndings. An up-staging eect by the investigation of a
possibly maximal number of lymph nodes could not be detected.
Disclosure Statement: e authors declare no conict of interest.
738
Can neoadjuvant chemoradiation (nCRT) be omitted in
patients with MRI-assessed, negative circumferential
resection margin in cT3 rectal cancer with multimodal
treatment - results of a prospective multi-center
observational study
Henry Ptok1; Frank Meyer2; Ingo Gastinger3; Benjamin Garlipp3
1Dept. of General and Abdominal Surgery, Municipal Hospital (“Ernst-von-
Bergman-Klinikum”), Potsdam, Deutschland
2Dept. of General, Abdominal, Vascular and Transplant Surgery, Otto-von-
Guericke University at Magdeburg with University Hospital, Magdeburg,
Deutschland
3Institute of Quality Assurance in Operative Medicine, Otto-von-Guericke
University at Magdeburg, Magdeburg, Deutschland
Aim: To determine whether nCRT can be omitted in patients with MRI-
assessed cT3-rectal cancer and a negative mrCRM undergoing good-
quality TME.
Method: By means of a nationwide registry (n=43.147; prospective
multi-center observational study), patients with cT3-rectal cancer <12cm
from the anal verge with a negative (>1mm) MRI-assessed circumfer-
ential margin(CRM) undergoing radical resection from 2006-2008 were
selected. Overall, 87 patients were available for nal analysis (TME-alone,
n=25; nCRT+TME, n=62). Groups were balanced for age, sex, and ASA
score, with a non-signicant predominance of males in the nCRT+TME
group. Local and distant recurrence rates were compared between patients
undergoing primary surgery (TME-alone) vs. neoadjuvant chemoradia-
tion+surgery (nCRT+TME).
Results: In the TME-alone group, tumors were located closer to the anal
verge (p=0.018) and demonstrated a smaller minimal circumferential dis-
tance from the resection margin (p=0.036).
TME quality was comparable, as was median follow-up (48.9 vs. 44.9
months, p=0.268). Local recurrences occurred at a similar rate in the
TME-alone (n=1, 5.3%) and nCRT+TME groups (n=3, 5.5%) (p=0.994)
and were diagnosed at 10 months (TME-alone) and at 8, 13, and 18
months (nCRT+TME). Distant recurrences occurred in 28.9% and 17.4%,
respectively (p=0.626).
Analysis was limited to cT3-cancers with a negative mrCRM. In addition,
caution is required when appraising these results because of the limited
number of subjects, which adds uncertainty to the statistics.
Conclusions: In this cohort of patients with rectal cancer located <12 cm
from the anal verge and a negative mrCRM undergoing adequate TME,
omission of nCRT had no impact onto the local recurrence rate.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 69
742
Value of research on clinical care in oncological surgery using
the example of rectal cancer
Frank Meyer1; Roland S. Croner2; Hans Lippert2
1Dept. of General, Abdominal, Vascular and Transplant Surgery, Otto-von-
Guericke University at Magdeburg with University Hospital, Magdeburg;
Deutschland
2Institute of Quality Assurance in Operative Medicine, Otto-von-Guericke
University at Magdeburg, Magdeburg; Deutschland
In the process of the implementation of novel diagnostic and therapeutic
modes and procedures, data obtained in area-wide multi-center obser-
vational studies along the establishing period of time are indispensable.
is can be impressively detected considering the development of rectal
cancer surgery in Germany over a 10-years study period based on original
data from the Institute of Quality Assurance in Operative Medicine, Otto-
von-Guericke University at Magdeburg.
From 01/01/2000 to 12/31/2010, overall 33,724 patients with rectal cancer
were registered in Germany and evaluated according to quality assurance
aspects.
e main focus was directed onto the current trends, such as
colonoscopy-screening, MRI (assessing involvement of the circumferen-
tial resection margin [CRM]), endoscopic ultrasonography, neoadjuvant
treatment conzepts, total mesorectal excision [TME] and laparoscopy–
assisted surgical interventions as well as the early postoperative (rather
surgical/ operative) results and oncological long-term outcome.
References:
1. Gastinger I, Lippert H, Köckerling F, Dralle H (ed.). Chirurgische Qualitäts-
sicherung - Ergebnisse der klinischen Versorgungsforschung. eBook (2021)
http://www.aninstitut.de/de/Home.html [Zugri: 31. 08.2021]
2. Ptok H, Mundt A, Lippert H, Gastinger I. Rektumkarzinomchirurgie in
Deutschland – eine 10-Jahres-Übersicht auf der Grundlage der Daten des
AN-Instituts für Qualitätssicherung in der operativen Medizin gGmbH an
der Otto-von-Guericke-Universität Magdeburg. Zentralbl Chir 2013; 138 (4):
418–426
Disclosure Statement: e authors declare no conict of interest.
759
Multivisceral resection of advanced colon and rectal cancer:
A prospective multicenter observational study with
propensity score analysis of the morbidity, mortality and
survival #) - #) Initial data was published in Chirurgische
Allgemeine (issue 7+8/2021 published by “Kaden-Verlag”)
Hans Lippert1; Roland S. Croner1; Frank Meyer2; Ronny Otto1;
Karsten Ridwelski1
1Institute of Quality Assurance in Operative Medicine, Otto-von-Guericke
University at Magdeburg, Magdeburg, Deutschland
2Dept. of General, Abdominal, Vascular and Transplant Surgery, Otto-von-
Guericke University at Magdeburg with University Hospital, Magdeburg,
Deutschland
Aim: To analyze non-multivisceral resection (nMVR) vs. MVR ([partial]
resection of the tumor[Tu]-bearing organ along with resection of the
adherent adjacent organs or tissues) in terms of early postop. & long-term
oncological outcomes.
Method: Data of 25,321 patients (364 hospitals) who had undergone sur-
gery for CRC (UICC stages I–III) during a dened period were evaluated
in this prospective multicenter observational study.
Results: From 2008-2015, MVR rates were 9.9% (n=1,551) for colon
cancer (CA) & 10.6% (n=1.027) for rectal CA.
e MVR group had a high prevalence of intraop. (.,8%; 12.1%) & postop.
surgical complications (30.8 vs. 36.4%; each p<0.001).
Wound infections (colon CA: 7.1%) & anastomotic insuciencies (rectal
CA: 8.3%) frequently occurred aer MVR.
Morbidity rates of the MVR groups were also determined (43.7 vs. 47.2%).
Hospital lethality was 4.9% in the colon CA-related MVR group & 3.8%
in the rectal CA-related MVR group & was signicantly increased com-
pared with those of the nMVR group (both p<0.001). Results of the MPA
showed that the morbidity in both MVR groups (colon CA: 42.9 vs. 34.3%;
rectal CA: 46.3 vs. 37.2%; each p<0,001) was signicantly increased.
Hospital lethality tended to increase in the colon CA-related MVR group
(4.8 vs. 3.7%; p=0.084), while it signicantly increased in the rectal
CA-related MVR group (3.4 vs. 3.0%; p=0.005).
Moreover, 5-yr overall survival rates were 53.9% (nMVR: 69.5%; p<0.001)
in the colon CA group & 56.8% (nMVR: 69.4%; p<0.001) in the rectal CA
group.
Risk factors common to both Tu types were advanced age (>79 yr), pT
stage, sex & morbidity (each hazard ratio: >1; p<0.05).
Conclusion: MVR allows curation by R0 resection with adequate long-
term survival. For colon or rectal CA, MVR tended to be associated
with reduced 5-yr overall survival rates (signicant only for pT4 colon
CA based on the MPA results, not shown), as well as, with a signicant
increase of morbidity in both Tu entities. In the overall data, MVR was
associated with signicant increases in hospital lethality, as indicated by
the MPA (signicant only for rectal CA).
Disclosure Statement: e authors declare no conict of interest.
761
Distinct mircobiomes in right- and left-sided colon cancer
Melanie C. Langheinrich1, Stefan Wirtz2, Barbara Kneis3, Klaus Weber4,
Maximilian Brunner4, Christian Krautz4, Jonel Trebicka5, Abbas Agaimy6,
Robert Grützmann4, Stephan Kersting1
1Universitätsmedizin Greifswald, Klinik für Allgemeine Chirurgie, Viszeral-
Thorax- und Gefäßchirurgie, Greifswald, Deutschland
2Universitätsklinikum ERLANGEN, FORSCHUNGSABTEILUNG Medizinische
Klinik1, Erlangen
3Universitätsklinikum Erlangen, Medizinische Klinik, Erlangen, Deutschland
4Universitätsklinikum Erlangen, Klinik für Allgemein- und Viszeralchirurgie,
Erlangen
5Universitätsklinikum Frankfurt, Sektion Translationale Hepatologie,
Medizinische Klinik 1, Frankfurt
6Universitätsklinikum Erlangen, Institut für Pathologie, Erlangen
Background: Colorectal cancer (CRC) is the third leading cause of cancer
death worldwide. Biologically CRC is a heterogeneous group. e patho-
genesis is complex and includes various genetic and epigenetic alterations.
It is widely accepted that tumor location (right- le-sided colon cancer,
RSCC, LSCC) is a crucial factor in determining disease progression and
inuences disease management. e rate of CRC rises among people aged
under 50. Changes in the incidence of a disease by generation, suggests
that the cause is environmental rather than biological. A number of envi-
ronmental factors play a role in carcinogenesis, including the microbiome.
Methods: e study population consists of 41 patients (RSCC 24, LSCC
17) from the prospective Erlanger microbiome study. Microbiota proles
(tumor; proximal resection margin (ileum, healthy colon), distal resec-
tion margin (healthy colon, rectum) and stool) were characterized by
amplication of the V3/V4 region of the 16SrRNA gene followed by deep
sequencing and biostatistical analysis.
Result: e overall structure of the microbiome was signicantly dierent
(alpha diversity Observed index: p value< 0.001) and beta diversity (PCoA:
p value< 0.001). e stool microbiome only partly reects the microbiome
of CC. e tumor microbiome of RSCC and LSCC showed a signicantly
dierent diversity (Chao1 index: p value: 0.01). Linear discriminant anal-
ysis (LDA) coupled with eect size measurements (LEfSe) was applied
to determine key taxa and 10 genera were identied. Furthermore, we
revealed a tumor-microbiome-ileal microbiome association.
Discussion: e microbiome puzzle is far from being solved. Most
microbiome studies used fecal rather than tumor or mucosal samples
and considered CRC as one disease group. Compositional alterations in
the microbiome are not restricted to dierent microhabitats, they dier
between RSCC and LSCC.
Conclusion: Collectively, our results provide new insights into the com-
plex microbiome landscape of CC.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts70
793
Does intestinal anastomosis in resection of colon cancer have
a signicant impact onto long-term survival?
Frank Meyer1, Ellen Hajduk2, Karsten Ridwelski2
1Dept. of General, Abdominal, Vascular and Transplant Surgery, Otto-von-
Guericke University at Magdeburg with University Hospital, Magdeburg,
Deutschland
2Institute of Quality Assurance in Operative Medicine, Otto-von-Guericke
University at Magdeburg with University Hospital, Magdeburg, Deutschland
Ziel: Analyse d. Einusses der Op-Technik (-/+ Darmanastomose)
& -Dringlichkeit von planbarer vs. Notfall-Op auf das frühpostop.
(Morbidität/Letalität) & Langzeit-onkochir. Outcome (5-J-Gesamt-/-Tu-
freies Überleben sowie -Lokalrezidivrate)
Methode: Prospektive multizentr. Observat.-Studie z. Erfassung aller
konsekutiven Patienten(Pat.) mit primärem Colon-CA
Ergebnisse: Von 2010–2016 wurden 14.466 Pat. erfasst (717 [4,96%] in
matched-pair”-Analyse einbezogen). 12.620 Pat. (87,2%) wurden elek-
tiv operiert unabhängig davon, ob eine Darmanastomose od. ein Anus
praeter(AP) angelegt wurde; Notfall - mehrheitlich (n=1.332 Pat.; 72,1%)
Darmanastomose möglich vs. 514 Individuen (27,9%) mit Notfall-OP,
die einen AP erhielten (noch seltener b. geplant op. Pat. AP erforderlich:
n=366 [3%]).
Pat., die eine AP-Anlage erhielten (wesentl. Einuss des präop. AZ)
erhielten od. im Notfall operiert wurden, wiesen ein nachteilig-
eres Risikoprol (art. Hypertonie, Diab. mell., kardiale od. renale
Nebenerkrankg.) auf - was nicht zuletzt die Diskontinuitätsresektion mit
rechtfertigte - und entwickelten häuger Komplikationen.
Neben der postop. Letalität (insbes. auch auf die allg. Komplikationsrate
zurückzuführen) wurden als wichtigste Ein.-Faktoren auf das
Langzeitüberleben Alter & Tu-Stadium sowie der R-Status ermittelt - je
fortgeschrittener der Tu, desto geringer el das Langzeitüberleben aus.
Die Kaplan-Meier-Kurven für die Op-Technik & Dringlichkeit zeigten
in der matched-pair-Analyse, dass Pat. mit gl. Tu-Stadium/Alter/
Risikofaktoren eine signif. bessere Überlebenschance haben, wenn sie
elektiv bzw. mit Darmanastomose operiert werden.
Multivariable Analyse: Ältere Pat. mit (lediglich) einer AP-Anlage zeigten
ein besseres Outcome.
Schlussfolgerung: Es werden Lit.-Angaben zum signif. Zusammenhang zw.
op. Komplikationen & Letalität sowie Vorerkrankg. & Komplikationsrate
bestätigt sowie, dass ältere Pat. in einem red. AZ (entspr. ASA-Scoring)
eher von einer Diskontinuitätsresektion (AP-Anlage) protieren wie auch
b. Fern-Mts.
Disclosure Statement: e authors declare no conict of interest.
799
The impact of the COVID-19 pandemic on the diagnosis and
medical care of colorectal cancer patients in Saxony - analyses
for the CancerCOVID consortium
Thomas Birkner1, Falko Tesch1, Martin Seifert1, Olaf Schoer1,
Jan Schildmann2, Anke Reinacher-Schick4, Jochen Schmitt3
1Zentrum für Evidenzbasierte Gesundheitsversorgung, Universitätsklinikum und
Medizinische Fakultät Carl Gustav Carus an der Technischen Universität Dresden,
Dresden
2Institut für Geschichte und Ethik der Medizin, Medizinische Fakultät der Martin-
Luther Universität Halle-Wittenberg, Uniklinikum Halle, Halle
3Zentrum für Evidenzbasierte Gesundheitsversorgung, Medizinische
Fakultät Carl Gustav Carus der Technischen Universität Dresden, Professur für
Sozialmedizin und Versorgungsforschung, Dresden
4Katholisches Klinikum Bochum, St. Josef Hospital Bochum, Ruhr Universität
Bochum, Medizinische Klinik V für Hämatologie und Onkologie mit
Palliativmedizin, Bochum, Deutschland
Background: e focus on treatment of COVID-19 patients during
the Sars-CoV-2 outbreak, lockdown measures and individuals’ anxiety
regarding potential infection when seeing a healthcare provider have
likely implications on the extent of diagnosis and quality of treatment of
non-COVID-19 patients. is hypothesis has been evaluated exemplarily
for the early detection, diagnosis and treatment of colorectal cancer in
Saxony within the framework of the CancerCOVID project.
Methods: e situation during 2020 was compared with the situation
before the Sars-CoV-2 pandemic (i.e., 2019). e evaluation is based
on pseudonymised routine statutory health insurance data for Saxony
including more than 50% of the population.
Result: A main nding was the drop in the number of diagnosis of new
colorectal cancer cases between 2019 and 2020 (i.e., 1797 versus 1352).
Furthermore, the per-patient rate of surgeries for incident colorectal
cancer cases increased slightly (2.4 to 2.5), as did the rate of intravenous
(IV) cytostatics administration (2.2 to 2.4) and radiation therapy (1.1
to 1.4). e per-patient rate of surgeries for prevalent colorectal cancer
patients remained constant (0.3), as did the rate of radiation therapy (0.2).
However, the per-patient rate of IV cytostatics for prevalent colorectal
cancer patients decreased from 1.7 to 1.4. e results of analyses pertain-
ing to cancer screenings and mortality are available as well.
Discussion: It is likely that reduced screenings and fewer contacts with
healthcare providers due to the pandemic led to the drop in new diagno-
sis. e reasons for the small numeric increases in the rates of procedures
per incident patient versus the largely at trajectory in the rate of health
care services for prevalent cases require further exploration.
Conclusion: COVID-19 was associated with changes in the provision of
health care especially for cancer patients, which should be taken into con-
sideration in the resource planning when preparing for another pandemic
or public health emergency.
Disclosure Statement: e authors declare the following: consultant
808
In vitro and in vivo characterization of the novel PFKFB3
inhibitor KAN0438757 in colorectal cancer
Tina Goldhardt1; Marcus Edelmann1; Tiago de Oliveira1; Annalen
Bleckmann2; Kerstin Menck2; Lutz Ackermann3; Torben Rogge3; Tim
Beissbarth4; Michael Ghadimi1; Lena-Christin Conradi1
1Universitätsmedizin Göttingen, Klinik für Allgemein-, Viszeral-, und
Kinderchirurgie, Göttingen, Deutschland
2Universitätsklinikum Münster - UKM, Medizinische Klinik A, Münster,
Deutschland
3Georg-August-Universität Göttingen - Fakultät für Chemie, Institut für
organische und biomolekulare Chemie, Göttingen, Deutschland
4Universitätsmedizin Göttingen, Institut medizinische Bioinformatik, Göttingen,
Deutschland
Background: Rectal cancer is routinely treated by neoadjuvant radio-
chemotherapy followed by surgical resection. Less than 20% of patients
show a complete pathological response upon this regimen. It was previ-
ously shown that glycolytic inhibition via targeting of PFKFB3 results in
tumor vessel normalization. A novel PFKFB3 inhibitor (KAN0438757)
was shown to have radio- and chemosensitizing capacity. We here eval-
uate KAN0438757 in vitro and in vivo in combination with standard
chemotherapy.
Methods: Human CRC cell lines (HCT-116, HT-29) and endothelial cells
(HUVECS) were subjected to KAN0438757 alone or in combination with
chemotherapy. Proliferation, cell death, migration and invasion were
assessed. KAN0438757 was also tested in healthy C57BL/6 mice for its tox-
icity prole before performing treatments in PDX using NOD-SCIDprkdc
mice to explore eects on tumor growth and tumor vascularization.
Result: We found a concentration dependent antiproliferative eect of
KAN0438757. Migration as well as the invasive capacity were signi-
cantly reduced, independently of the antiproliferative eect. KAN0438757
alone showed no high-grade toxicity in healthy mice. When combining
KAN0438757 with chemotherapy we observed a synergistic anti-tumor
eect and signs of tumor vessel normalization.
Discussion: As PFKFB3 is overexpressed in CRC but also in endothe-
lial cells, we speculated that KAN0438757 mainly targets the tumor while
leaving non-transformed cells unaected. Since high-dose inhibition of
PFKFB3 can aect tumor cells, low-dose treatment leads to tumor vessel
normalization. When using a low concentration of KAN0438757, eects
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 71
on tumor growth were visible in combination with chemotherapy, but not
upon KAN0438757 alone.
Conclusion: KAN0438757 showed a clear antiproliferative eect in rectal
cancer cells and PDX without being overly toxic in vivo. It showed promis-
ing synergistic ecacy when used in combination with chemotherapy and
therefore should be further tested in vivo.
Disclosure Statement: e authors declare no conict of interest.
815
Molecular consensus subtyping of colorectal carcinoma In
liver and brain metastases
Carolin Krekeler1; Barnabas Irmer1; Suganja Sivaloganathan1;
Kerstin Menck1; Micha Peeck1; Darius Wlochowitz2; Lena-Christin
Conradi3; Astrid Wachter2; Michaela Bayerlova2; Alexander Wol2;
Hans-Ulrich Schildhaus4; Christine Stadelmann-Nessler5;
Martin Proescholdt6; Kia Homayounfar3; Tobias Pukrop6,7; Tim Beissbarth2;
Annalen Bleckmann1,7
1University Hospital Münster, Dept. of Medicine A, Hematology, Oncology and
Pneumology
2University Medical Center Göttingen, Dept. of General, Visceral and Pediatric
Surgery
3University Medical Center Göttingen, Dept. of Medical Statistics
4University Hospital Essen, Institute for Pathology
5University Medical Center Göttingen, Dept. of Neuropathology
6University Medical Center Regensburg, Dept. of Internal Medicine III,
Hematology and Medical Oncology
7University Medical Center Göttingen, Dept. of Hematology and Medical
Oncology
Background: Inter-metastatic heterogeneity in patients suering from
colorectal carcinoma (CRC) is discussed as a cause for diverse clinical
outcomes. erefore, this study aimed to identify prognostically relevant
characteristics of CRC-derived metastatic tissue samples from brain and
liver at the transcriptome and proteome level. ereby we additionally
strived to better understand processes of metastatic organotropism to
ultimately nd new potential cancer vulnerabilities for targeted therapy
in CRC patients.
Methods: Tissue samples from 61 CRC patients with liver or brain metas-
tases were collected and analyzed by RNA sequencing (RNA-Seq) as well
as reverse phase protein array (RPPA). e expression levels of selected
dierentially expressed genes were further quantied by RT-qPCR and
immunohistochemistry. All metastases were annotated according to the
previously described consensus molecular subtype (CMS) classication.
e resulting CMS proles were correlated with the overall survival of
CRC patients.
Result: CRC metastases in liver and brain were signicantly dierent (p
<0.001) when comparing the corresponding RNA and protein signatures.
Liver metastases showed enriched amounts of the mesenchymal CMS4
subtype, which was shown to be prognostically favorable (p = 0.018) with
a 3-year survival of 73.3% of patients aer metastases resection. In con-
trast, most brain metastases were assigned to the metabolic CMS3 sub-
type, which was further conrmed by quantifying the expression levels
of selected metabolic genes on RNA and protein level within the corre-
sponding tissue samples.
Conclusion: Transcriptomic evaluation and CMS-based classication of
dierent CRC metastases revealed an inter-metastatic heterogeneity with
organ-specic CMS-signatures and evident impact on patients survival.
We identied a metabolic signature of CRC-derived brain metastasis that
might be exploited by upcoming studies to nd new therapeutic targets
for those patients.
Disclosure Statement: e authors declare no conict of interest.
864
Pathological function of neutrophil extracellular traps in
human colon cancer
Antonia Margarethe Stehr1; Guangxia Wang1; Richard Demmler1;
Marc P Stemmler2; Philipp Tripal3; Carol I Geppert4; Susanne Merkel5;
Martin Herrmann6,7; Michael Stürzl1,8
1Friedrich-Alexander University (FAU) Erlangen-Nürnberg and
Universitätsklinikum Erlangen, Department of Surgery, Division of Molecular
and Experimental Surgery, Translational Research Center, Erlangen, Deutschland
2Friedrich-Alexander University (FAU) Erlangen-Nürnberg, Nikolaus-Fiebiger
Center for Molecular Medicine, Department of Experimental Medicine I,
Erlangen, Deutschland
3Friedrich-Alexander University (FAU) Erlangen-Nürnberg, Optical Imaging
Centre, Erlangen, Deutschland
4Friedrich-Alexander University (FAU) Erlangen-Nürnberg and
Universitätsklinikum Erlangen, Institute of Pathology, Erlangen, Deutschland
5Friedrich-Alexander University (FAU) Erlangen-Nürnberg and
Universitätsklinikum Erlangen, Department of Surgery, Erlangen, Deutschland
6Friedrich-Alexander University (FAU) Erlangen-Nürnberg and
Universitätsklinikum Erlangen, Department of Internal Medicine 3, Erlangen,
Deutschland
7Friedrich-Alexander University (FAU) Erlangen-Nürnberg and
Universitätsklinikum Erlangen, Deutsches Zentrum für Immuntherapie (DZI),
Erlangen, Deutschland
8Universitätsklinikum Erlangen, Comprehensive Cancer Center Erlangen-EMN,
Erlangen, Deutschland
Background: Neutrophil extracellular traps (NETs) are extracellular
structures formed by neutrophils, consisting of their DNA and proteins.
Although originally described as a defense mechanism to kill bacteria,
NETs have been reported to negatively inuence various kinds of diseases,
including cancer. However, especially data on intra-tumor NET presence
is very limited and the association of tissue NETs with clinically relevant
parameters remains unclear. We therefore sought to establish and vali-
date a robust method of intra-tumor NET detection and investigate the
relation between tissue NET presence and clinical features of colorectal
carcinoma (CRC) patients.
Methods: NET presence in colon cancer tissues from 85 patients was
assessed by staining formalin-xed paran-embedded tissue sections
for neutrophil elastase, citrullinated histone H3 (H3cit), histone H2B
and extracellular DNA (using a large IgM anti-DNA antibody). Staining
was evaluated by laser-scanning microscopy and partly by high-resolu-
tion stimulated emission depletion (STED) microscopy. Further, CRC cell
lines were incubated with in vitro generated NETs from human isolated
neutrophils to investigate direct eects of NETs on cancer cells.
Result: H3cit was sucient to detect intra-tumor NET formation, which
was commonly present in colon cancer tissues (37/85, 44%). In most
cases, tumor inltrating NETs were located in both the tumor center and
the invasive front or in the tumor center only. Remarkably, the presence
of NETs signicantly correlated with high tumor grades and locoregional
metastases. In addition, NETs were found to induce migration, pseudo-
podia formation and epithelial-mesenchymal transition (EMT) in CRC
cells, in vitro.
Discussion: We oer an easy-to-use tool for the evaluation of intra-tumor
NET presence. Further, our results support the association of tumor inl-
trating NETs with unfavorable clinical characteristics, indicating that they
might contribute to tumor progression.
Conclusion: NETs present as a promising therapeutic target in CRC.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts72
866
Upfront surgery in upper rectal cancer– TME or
PME? - Impressions from a single GAST-05-study site
Laura Regina Werle1, Andreas Leha2, Friederike Braulke3,4,
Johanna Kreutzer1, Tatiana Grammatikopoulou1, Charlotte de Boer1,
Torsten Liersch1
1Department of General, Visceral and Pediatric Surgery, University Medical
Center of the Georg August University of Göttingen, Göttingen, Deutschland
2Institute for Biostatistics and Biometry, University Medical Center of the Georg
August University of Göttingen , Göttingen, Deutschland
3Department of Hematology and Medical Oncology, University Medical Center
of the Georg August University of Göttingen, Göttingen, Deutschland
4Comprehensive Cancer Center, University Medical Center of the Georg August
University of Göttingen, Göttingen, Deutschland
Background: To evaluate whether total (TME) or partial mesorectal
(PME) excision is required for stage II/III cancer in the upper rectum (≥
12 cm above anal verge) according to the GAST-05 randomized multi-
center phase II trial (ISRCTN35198481)
Methods: Surgery was performed in 98 (median age: 69 years) partici-
pants of the most recruiting GAST-05-study site randomized to TME
(control) vs. PME (experimental). Based on standardized staging, surgical
procedures were evaluated in terms of feasibility, peri-/postoperatively
determined quality, and of acute and/or long-term adverse events using
NCI-CTCAE-criteria (vs 3.0). Various clinicopathological parameters
(such as safety margin, circumferential resection margin (CRM), conver-
sion between TME and PME, technique of anastomosis) were included in
survival analyses using Logrank test, Kaplan-Meier estimator, and mul-
tivariable Cox proportional hazard regression models to test interaction
eects of selected predictors.
Result: TME (44.9%) and PME (55.1%) were performed in 82.7, 16.3 and
1%, respectively, with good, moderate, or poor quality. R0 and negative
CRM (≥ 2 mm) status were achieved in 95.5, 98.1, 72.7, and 66.7% aer
TME and PME, respectively. e 60-day mortaliy was 1.0%. During the
follow-up period of 60 months, 264 adverse events (AEs) were docu-
mented, 179 aer TME and 54 aer PME. e most frequently AEs (grade
1 to 4) were diarrhea (TME: 49.1%; PME: 42.9%), erectile dysfunction
(TME: 21.2%; PME: 25.8%) and fecal incontinence (TME: 20.1%; PME:
15.2%). Restrictive mean value of RFS for stage II patients (108.9 months)
was signicantly better than for stage III (78.7 months; p<0.001). Tumor
inltration depth (< 5 vs. ≥ 5 mm; p = 0.031) and age (p = 0.005) had an
impact on RFS (univariable models). Results from the multivariable sur-
vival analyses will be presented at the DKK.
Discussion: Surgical quality and safety margins in PME have an impact
on RFS, PME seems to be not inferior to TME in upper rectal cancer.
Conclusion: TME is associated with more postsurgical complications vs.
PME.
Disclosure Statement: e authors declare no conict of interest.
867
Treatment Patterns in Patients with BRAF V600E mutant
metastatic colorectal carcinoma: German and Austrian
Subgroups from the CAPSTAN CRC retrospective study
Isabel Virchow1; Susanna Hegewisch-Becker2; Arndt Nusch3;
Lutz Jacobasch4; Gerald Prager5; Jörg Tschmelitsch6; Manfred Welslau7;
Thomas Wol8; Frank Reichenbach9; Dirk Arnold10
1Department of Medical Oncology, West German Cancer Center, University
Hospital Essen, Essen, Deutschland
2Hämatologisch-Onkologische Praxis Eppendorf (HOPE), Hamburg, Deutschland
3MVZ für Hämatologie und Onkologie, Ratingen, Deutschland
4Gemeinschaftspraxis Hämatologie und Onkologie, Dresden, Deutschland
5Medical University of Vienna, Vienna, Österreich
6Hospital Barmherzige Brüder, St. Veit an der Glan, Österreich
7Oncological Practice Aschaenburg, Aschaenburg, Deutschland
8OncoResearch Lerchenfeld, Hamburg, Deutschland
9Pierre Fabre Pharma GmbH, Freiburg, Deutschland
10Asklepios Tumorzentrum Hamburg, AK Altona, Hamburg, Deutschland
Background: BRAF V600E mutant metastatic colorectal cancer (mCRC)
is associated with a poor prognosis. Current European guideline recom-
mendations for this population are mostly based on small cohorts due to
limited clinical data.
Methods: CAPSTAN is a retrospective study evaluating rst-line treat-
ment patterns, eectiveness and safety of BRAF V600E-mutant mCRC
treatment in 7 European countries initiated between 2016 and 2018. Here,
systemic treatment patterns of the German (D) and Austrian (A) sub-
groups were analyzed.
Result: 49 pts (D/A: N [%]: 45[18]/4[2]) were enrolled in D and A with
amedian age of 66 (D) and 62 years (A). In D and A, ca. half of the tumors
were right-sided and MSI-high status was noted for 27% of pts in D. Main
regimens in 1st-line were folinic acid/uorouracil (FOLF) and oxaliplatin
(OX) (FOLFOX) + bev (D/A [%]: 36/25), FOLFOX alone (D 18%), FOLF
plus irinotecan (IRI) (FOLFIRI) + bev (D/A [%]: 13/50), or FOLFOXIRI +
bev (D/A [%]: 13/25). CT + anti EGFR (cetuximab or panitumumab) was
used in 9% of pts in D. Median duration of 1st-line treatment was 4.7 and
2.2 months (D/A). 49% of pts enrolled in CAPSTAN overall had at least
1 treatment-related, adverse event considered relevant in 1st-line (RAE),
including diarrhea (12%), peripheral neuropathy (8%), neutropenia (7%),
asthenia (6%), and nausea (6%). Most RAEs occurred under triplet CT +/-
targeted therapy (TT; anti VEGF or anti EGFR). 62 and 75% of pts con-
tinued to at least 2nd-line (D/A). Details on 2nd and further treatment lines
and comparison to the CAPSTAN total population will also be reported.
Discussion: Based on the CAPSTAN study, 1st line treatment of BRAF
V600E-mutant mCRC pts in D and A mainly consists of CTs + targeted
agents. Both anti-VEGF and anti-EGFR are used in this treatment setting.
Most RAEs were associated with TT + triplet CT backbone.
Conclusion: In line with updated DGHO guideline recommendations,
doublet CT was used as the preferred backbone for anti-VEGF treatment.
Indication of source
1 Virchow I. et al., DGHO congress 2022, abstract #28
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organiser KUKM GmbH and KUKM
can disclose them if needed.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 73
Poster
Gastrointestinal (Colorectal) Cancer
897
Successful introduction of a point mutation into the genome
of a primary colon cancer cell line using CRISPR base editing
technology
Bakr Mustafa; Abdelouahid Maghnouj; Stephan Hahn
Ruhr universität Bochum, Department of Molecular Gastrointestinal Oncology,
Bochum, Deutschland
Novel CRISPR/Cas9 genome base editing technology is a powerful DNA
editing. Many eorts have been made to investigate the editing eciency
of CRISPR base editing system. However, the editing eciency of stably
expressed base editors in primary tumor cell lines is not well studied due
to lentivirus packaging limitations and the low transduction eciency of
primary tumor cell lines.
Here, we generated a lentiviral adenine base editor vector that has a ex-
ible NGN PAM recognition site. To study its editing eciency, we have
developed a GFPstop reporter gene which was subsequently introduced
into the genome of the primary cell line. we have used a 50x concentrated
lentivirus for the delivery of the adenine base editor. we compared the
editing eciencies of a non-inducible sgRNA expression vector and an
inducible sgRNA.
We found a highly stable expression of the adenine base editor in a pri-
mary colon cancer cell line. In addition, the adenine base editor success-
fully modied the endogenous GFPstop transgene to reverse the stop
codon into glutamine (TAG>CAG). FACS detected 15% GFP positive
cells using non-induced sgRNA three days aer transduction and up to
5% GFP positive cells were found using an inducible sgRNA aer three
days of induction with doxycycline. To investigate the ability of the ade-
nine base editor to target an endogenous gene, we targeted KRAS codon
61. Adenine base editor successfully introduced KRAS Q61R mutation
CAA>CGA. We were able to detect 1.5% allele frequency for the KRAS
Q61R mutated allele using ddPCR. Sanger sequencing conrmed the
introduction of KRAS Q61R point mutation.
Our study demonstrates the ecient introduction of a point mutation in
the genome of primary colon cancer cell line using a stable expression
of CRISPR/Cas9 base editing system. High virus concentration and the
use of a non-inducible sgRNA vector are potential important parameters
for ecient editing. is strategy should be useful to study the biology of
oncogenic mutations under the control of its endogenous promoter with-
out the need for classical transgenic animal technology.
Disclosure Statement: e authors declare no conict of interest.
947
Findings in a young group with familial colorectal risk: Results
of the FARKOR study
Alexander Crispin1; Sabine Homann1; Raael Rehms1; Doris Lindörfer1;
Lara Hallsson2; Nikolai Mühlberger2; Beate Jahn2; Uwe Siebert2;
Gaby Sroczynski2; Ulrich Mansmann1
1IBE, LMU München, München, Deutschland
2Institute of Public Health, Medical Decision Making und Health Technology
Assessment, UMITPrivate University for Health Sciences, Medical Informatics
and Technology, Hall i. Tirol, Österreich
Purpose: Colorectal cancer (CRC) screening in Germany starts at age 50.
As there is evidence that individuals with a family history of CRC have an
increased risk of developing CRC before age 50, screening for this group
should start earlier. FARKOR (FAmily Related COlorectal cancer Risk)
evaluates the clinical and economic eects of a risk-adapted screening
program for CRC in individuals between 25 and 50 years of age.
Methods: Our nal analysis assesses the eects of FARKOR in a popu-
lation-based prospective cohort study. e program was open to mem-
bers of the statutory health insurance in Bavaria (aged 25 to 49 years)
between October 2018 and March 2021. Participants entered the study
through their physicians or a public campaign. Additionally, sickness
funds contacted recently diagnosed CRC patients to inform them about
the potentially increased CRC risk of their relatives. Trained doctors clas-
sied participants as potential risk carriers or as inconspicuous. Potential
risk carriers were invited to make a shared decision with their doctors on
1) an immunological fecal occult blood test (iFOBT) or 2) a screening
colonoscopy.
Results: During the program, 25,848 eligible patients joined the pro-
gram. Among the 5,769 identied potential risk carriers, 1,188 received
an iFOBT, while 1,595 underwent a colonoscopy. 287 patients with ade-
nomas (76 of them advanced) were identied (18.0% of the participants).
Four patients had CRC (0.25%). Record linkage with insurance data
revealed these numbers to be underestimates, since screening procedures
initiated by FARKOR but performed outside the program were not docu-
mented in the study database. Colonoscopy complications were limited to
four bleedings that could be treated conservatively.
Conclusions: Our results show good adherence to the proposed screen-
ing measures. Detection rates resemble screening programs in older
populations.
Disclosure Statement: e “German Innovation Fund” of the Federal Joint Com-
mittee (G-BA) supports this work: 01NVF17026. e authors declare no conict
of interest.
955
Consistency of familial risk proles between questionnaire
and interview based risk assessment in a screening
population: Results from the FARKOR study
Ulrich Mansmann1; Sabine Homann1; Raael Rehms1; Doris Lindörfer1;
Lara Hallsson2; Beate Jahn2; Nikolai Mühlberger2; Gaby Sroczynski2;
Uwe Siebert2; Alexander Crispin1
1IBE, LMU München, München, Deutschland
2Institute of Public Health, Medical Decision Making und Health Technology
Assessment, UMITPrivate University for Health Sciences, Medical Informatics
and Technology, Department of Public Health, Health Services Research and
Health Technology Assessment, Hall i. Tirol, Österreich
Background: FARKOR1 is a population based observational study to
motivate young persons with familial CRC risk (fCRC) to prevent CRC.
e study uses a two-step selection process to asses fCRC by a ques-
tionnaire and an interview-based evaluation. It was of interest to study
the consistency of risk assessments between both steps and information
gained from family trees (FT).
Methods: FARKOR recruited young members of the statutory health
insurance in Bavaria between October 2018 and March 2021. Trained
doctors classied participants as potential risk carriers starting with a
questionnaire2 (Q), followed by an interview (I).
Result: A total of 25,848 subjects participated (70.0% female, mean age
37.2 y) of whom 5,769 (22.3%) had a Q based fCRC (70.0% female, mean
age 39.0 y). About 13.7% documented only 2nd grade relatives, 6.1% only
1st grade relatives, and 2.5% 1st and 2nd grade relatives with CRC diagnosis.
A total of 3,162 (58.0%, n=5,769) subjects underwent I based risk assess-
ment. e criteria based consistency between Q und I ranged between
74.4% and 78.7%. A total of 2504 FTs were documented. For 5 criteria,
consistency between Q and FT ranged between 63.0% and 87.1% and
between I and FT between 79.9% and 92.5% respectively.
Discussion: Agreement between Q and I based assessment is about 75%.
Compared to FT documented information during the interview, Q based
consistency is less than the I based risk assessment which was simultane-
ously assessed with the FTs. e prevalence of familial CRC risk as found
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts74
in the FARKOR population cannot be generalized because of unclear
selection mechanisms with which participants were recruited.
Conclusion: e observed inconsistencies demonstrate the need to train
persons to be screened as well as medical personnel in assessing objective
disease information from family histories.
Reference:
1. Homann S et al BMC Gastroenterol 2020,20(1):131. doi: 10.1186/s12876-020-
01247-6.
Disclosure Statement: e “German Innovation Fund” of the Federal Joint Com-
mittee (G-BA) supports this work: 01NVF17026. e authors declare no conict
of interest.
963
Intraoperative ICG uorescence identies colorectal liver
metastaseswith complete response after chemotherapy
Oliver Stöltzing
Elblandklinikum Riesa, Elblandkliniken, Allgemein- und Viszeralchirurgie,
Riesa,Deutschland
Background: Patients with multifocal colorectal liver metastases (CRLM)
oen receive systemic therapy prior to surgery. At the time of re-staging,
CRLM may become undetectable by imaging aer chemotherapy, i.e. dis-
appearing liver metastases (DLM). But DLM does not necessarily equal
pathological complete remission (CR). An increasing number of patients
with DLM is presented in tumor conferences, confronting surgeons with a
dicult dilemma: to resect or to not resect the original sites of DLM? e
aim of this investigation was to evaluate the role of ICG-uorescence in
liver surgery to identify colorectal DLM.
Methods: For ICG-analysis of CRLM and suspected CR, patients (n=3)
with initial multifocal disease received 5 mg of indocyanine green (ICG)
24-72h prior to laparoscopic surgery. Fluorescent – anatomy was visual-
ized by using the Storz ICG-system or Pinpoint/Stryker. Multiple acces-
sible lesions were excised per patient by minimal-invasive liver surgery.
Resected specimen were sectioned, photographed and histologically
examined.
Result: In all three patients with DLM, ICG-uorescence was able to iden-
tify the original metastatic sites. In one patient, excised lesions showed
persistent vital tumor cells. However, in 2 patients, histology revealed a
full pathological remission with no vital tumor areas within the excised
ICG-positive lesions.
Discussion: is is the rst report to demonstrate that colorectal liver
metastases preserve an ICG-positive rim aer pathological complete
remission. is nding can substantially contribute to dening the appro-
priate oncologic concept in patients with multifocal CRLM and DLM aer
chemotherapy. us, when identifying ICG-positive reference lesions with
pathological CR, a watch and wait strategy may rather be recommended
than major liver surgery of entire original sites of metastases.
Conclusion: ICG-uorescence is valuable for detecting occult CRLM aer
chemotherapy and may impact clinical decision making in liver surgery.
Disclosure Statement: e author declares no conict of interest.
1006
Role of oxaliplatin in multimodality treatment (MMT)
of rectal cancer – a single center experience
Beate Michels1; Torsten Liersch2; Johanna Kreutzer2; Timotheus Ritter2;
Andreas Leha3; Friederike Braulke4,5
1Universitätsmedizin Göttingen, Klinik für Gastroenterologie, gastrointestinale
Onkologie und Endokrinologie, Göttingen, Deutschland
2Universitätsmedizin Göttingen, Klinik für Allgemein-, Viszeral- und
Kinderchirurgie, Göttingen, Deutschland
3Universitätsmedizin Göttingen, Institut für medizinische Statistik, Göttingen,
Deutschland
4Universitätsmedizin Göttingen, Universitätskrebszentrum Göttingen,
Onkologisches Zentrum, Göttingen, Deutschland
5Universitätsmedizin Göttingen, Klinik für Hämatologie und medizinische
Onkologie, Göttingen, Deutschland
Background: Use of oxaliplatin (OX) in MMT for locally advanced ade-
nocarcinoma of the rectum (LARC) combined with 5-FU-based chemo-
radiotherapy (CRT, 50.4 Gy), total mesorectal excision (TME) and pre-/
postoperative chemotherapy (CTx) is still under debate. Its role in total
neoadjuvant treatment (TNT) needs to be claried.
Methods: 177 LARC patients (cUICC stages II-IV in 4, 91 and 5.1%,
respectively; tumor height: <12 cm above anal verge) were treated between
7/2006 to 6/2016 at a single center according to clinical trial protocols
in cohorts A (preopCRT▶TME▶ 5-FU; n=64), B (preopCRT+5-FU+
OX▶TME▶ FOLFOX; n=63) and C (preopCRT+5-FU+OX▶3 appli-
cations of FOLFOX▶TME; n=50). Feasibility, toxicity, compliance, and
ecacy of MMT were analyzed. In addition, clinicopathological parame-
ters were assessed for prognostic relevance using COX regression analyses
and uni-/multivariable survival models.
Results: CRT resulted in > 98.1% (12.2% dose adherence); CTC-AE-
grades ≥3 at <4.5%; compliance at 98%; adCTx at 77% (28% dose reduc-
tion). Cohort C had the lowest rate of CTC-AE grade ≥3. In cohorts A and
B, adCTx was also associated with low rate of CTC-AE grade ≥3 toxicity
(<8%). Outcomes aer TME showed R0-status in 96%, negative CRM
in 92% (≥2 mm), and a reduction in longitudinal tumor extent of >50%
(ypTE: ≤25 mm). Histopathologic staging revealed stages ypUICC-0-IV
in 14.5, 23.1, 27.7, 24.9, and 9.6%, respectively. Distant and local recur-
rences occurred in 31.3 and 5.4% (median 73-m follow-up), respectively.
Univariate analyses showed dierences in DFS for MMT-induced tumor
regression (p=0.001), ypCRM (p=0.002), ypTE (p=0.023) and ypUICC
status (p< 0.0009). Multivariate analysis revealed higher CSS for ypUICC
stages ≤II (p=0.007; HR: 0.31; 95% CI: 0.14-0.73).
Discussion: In future, early available stage should be used to adjust adCTx
to individual recurrence risk. However, patients with stages ≤II aer TNT
do not require further adCTx.
Conclusion: OX in MMT is safe, feasible, and leads to improved early
tumor regression, esp. In TNT, associated with good compliance and
survival.
Disclosure Statement: e authors declare no conict of interest.
1037
Analysis of colorectal cancer and adenoma microbiome
signatures and the application of machine learning
classication as a potential screening tool
Katarina Priselac1; Christian Jansen2; Catia Pacíco2; Barbara Sladek2;
Nikolaus Gasche2
1Technische Universität Wien, Fakultät für Technische Chemie, Institut für
Verfahrenstechnik, Umwelttechnik und technische Biowissenschaften, Wien,
Österreich
2Biome Diagnostics GmbH, Wien, Österreich
Background: Recent studies have shown a link between the develop-
ment of colorectal cancer (CRC) & the composition of a patients intes-
tinal microbiome. Since this cancer usually progresses from an adenoma
form, detection at an initial adenoma stage is crucial for increasing the
success rate of treatment. is study aims to identify microbial signatures
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 75
associated with CRC & adenoma and to optimize machine learning (ML)
algorithms for stool based early screening of CRC.
Methods: Datasets containing amplicon sequencing information from
healthy individuals & adenoma/CRC patients were obtained from pub-
licly available repositories and merged into a single meta-analysis dataset
containing 1786 samples. Dierential abundance (DA) analysis has been
conducted using the MaAsLin2 package. ML models were built in Python
using the sckit-learn library.
Result: DA analysis of CRC vs. healthy samples resulted in a total of 44
dierentially abundant taxa (q<0.05, abs(coe) > 1.5), 8 of which were
increased in CRC stool samples. Comparison of adenoma & healthy
samples revealed enrichment of one taxon in adenoma samples. e
best ML performance for CRC-healthy classication was obtained using
a Support Vector Machine model resulting in an area under the curve
(AUC) of 0.84 on the cross-validation and 0.80 on the test dataset. For
the adenoma-healthy distinction, the Light Gradient Boosted Machine
model achieved an AUC of 0.85 on the cross-validation and 0.72 on the
test dataset.
Discussion: DA analysis results between CRC & healthy samples match
with reported ndings. For the rst time, a large meta-analysis dataset
has been used for CRC and adenoma predicting purposes using machine
learning algorithms.
Conclusion: Results demonstrate the suitability of ML algorithms for the
development of microbiome-based solutions for non-invasive screening
of CRC and colorectal adenomas. Future aspects include comprehensive
interpretation of the created models to nd a universal microbial bio-
marker for CRC and colorectal adenomas.
Disclosure Statement: e authors declare no conict of interest.
1045
Impact of BOLD-100 on glucose metabolism and protein
glycosylation: role in resistance against the ruthenium
complex
Theresa Mendrina1,2; Dina Baier1,2; Beatrix Schoenhacker-Alte1,2;
Christine Pirker2; Thomas Mohr2; Petra Heeter2;
Bernhard K. Keppler1; Walter Berger2
1Institute of Inorganic Chemistry, University of Vienna, Vienna, Österreich
2Center of Cancer Research and Comprehensive Cancer Center, Medical
University Vienna, Vienna, Österreich
Cellular energy metabolism is reprogrammed in cancer to fuel prolifer-
ation. Identifying metabolic changes as vulnerabilities might open novel
approaches for resistance prevention or targeting. Sodium trans-[tetra-
chlorobis(1H-indazole)ruthenate(III)] (BOLD-100), a ruthenium-based
metal complex currently evaluated clinically, exerts strong metabolic
activities. Data published recently by our group showed deregulation of
the carbohydrate metabolism as direct response to and resistance factor
against BOLD-100. In fact, enhanced glycolytic activity as metabolic vul-
nerability was identied in BOLD-100 resistance, suggesting targeting of
glycolysis as a promising strategy to promote BOLD-100 anticancer activ-
ity. However, detailed information about the impact of BOLD-100 on gly-
colysis downstream pathways, such as pentose phosphate pathway and/or
hexosamine biosynthetic pathway (HBP), is still incomplete.In this study,
the activity of those pathways was investigated in BOLD-100-sensitive
versus -resistant colon and urothelial cancer cells by using specic phar-
macologic inhibitors.Resistant cell models showed resensitisation towards
BOLD-100 when HBP was inhibited using glutamine-fructose-6-phos-
phate amidotransferase or O-GlcNAc transferase inhibitors. Fittingly,
gene set enrichment analysis (GSEA) of whole-genome gene expression
data indicated signicant enrichment of the term “O-Glycan biosynthe-
sis” in resistant compared to parental cells. Especially, the rst enzyme
of O-glycosylation, N-acetylgalactosaminyltransferase, was upregulated
during acquisition of BOLD-100 resistance. Accordingly, this gene set was
signicantly downregulated in parental cells upon BOLD-100 treatment.
Currently, we concentrate on the impact of glycosylation on the mode of
action of BOLD-100 and vice versa, focusing on glycosylation of GRP78,
a known target of BOLD-100. In summary, targeting O-glycosylation rep-
resents a potential new approach to circumvent BOLD-100 resistance.
Disclosure Statement: e authors declare no conict of interest.
1069
Role of magnetic resonance imaging (MRI) in upper rectal
cancer (≥12 cm above anal verge, AV) – a single-center
experience
Andreas Leha1; Ali Seif2; Johanna Kreutzer3; Laura Werle3;
Timotheus Ritter3; Carsten-Oliver Sahlmann4; Torsten Liersch3
1Institut für Medizinische Statistik, Universitätsmedizin Göttingen, Göttingen,
Deutschland
2Institut für Diagnostische und Interventionelle Radiologie, Universitätsmedizin
Göttingen, Göttingen, Deutschland
3Klinik für Allgemein-, Viszeral- und Kinderchirurgie, Universitätsmedizin
Göttingen, Göttingen, Deutschland
4Klinik für Nuklearmedizin, Universitätsmedizin Göttingen, Göttingen,
Deutschland
Background: Pelvic MRI is well established in staging of advanced cancer
(stages ≥II) in the lower parts of the rectum (<12 cm above AV). In upper
rectal cancer (≥12 cm), its value is still unclear.
Methods: In this single-center project, staging with MRI, rES, and CT
was compared with outcomes aer upfront surgery (TME vs. PME) in 98
participants of the GAST-05 phase II trial (ISRCTN35198481). MRI accu-
racy (mrAC) was determined based on cancer stage (7th TNM/UICC-
classication). Parameters such as T, N, and UICC status, circumferential
resection margin (CRM), extramural vascular inltration (EMVI) were
analyzed for recurrence-free survival (RFS) using logrank test, Kaplan-
Meier estimator, and multiparametric Cox proportional hazard regression
models. MRI evaluations (MRI 2nd read) of tumor site, peritoneal reection
fold (PRF), and mrEMVI were then performed in 35 patients.
Results: Postsurgical staging revealed stages I to IV in 14.3, 43.9, 36.7 and
5.1%, respectively. mrAC was 79.3% for distinguishing stages ≥II vs. <II
and 74.5% and 85.1% for N status and stage (≥II), respectively (vs. 59.6%
and 72.3% with rES). In addition, MRI was superior to rES and CT in
describing CRM and EMVI. Using survival models in cohort A (n=47;
with MRI) vs. B (n=51; without MRI), patients age, stage ≥III, and T
status were shown to have signicant impact on RFS. MRI 2nd read revealed
that the PRF was signicantly closer to the AV and the aboral tumor mar-
gin was more distant in women (median 40 mm vs. 12.5 mm). mrAC in
EMVI was 48.6%, but the postulated positive mrEMVI (82.9%) was con-
rmed as positive pL-/V-/Pn status in only 11 specimens (31.4%). Patients
with a negative pL-/V-/Pn status had better CSS.
Discussion: Considering the surgical-anatomical landmarks, MRI staging
in upper rectal cancer could facilitate the decision for a more individual-
ized treatment.
Conclusion: Staging MRI combined with rES and rigid rectoscopy should
be used in patients with cancer in the upper rectum (≥12 cm) and recto-
sigmoid (>16 cm to 30 cm) to optimize preoperative assessment of T, N,
UICC, CRM, EMVI status and tumor location.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts76
1071
Adjuvant FOLFOX (adCTx) in cancer of the upper rectum (≥12
cm above AV) after upfront surgery – single-center experience
Charlotte de Boer1; Andreas Leha2; Julie Schanz3; Beate Michels4;
Johanna Kreutzer1; Timotheus Ritter1; Torsten Liersch1
1Klinik für Allgemein-, Viszeral- und Kinderchirurgie, Universitätsmedizin Göttingen,
Göttingen, Deutschland
2Institut für Medizinische Statistik, Universitätsmedizin Göttingen, Göttingen,
Deutschland
3Klinik für Hämatologie und Medizinische Onkologie, Universitätsmedizin
Göttingen, Göttingen, Deutschland
4Klinik für Gastroenterologie, gastrointestinale Onkologie und Endokrinologie,
Universitätsmedizin Göttingen, Göttingen, Deutschland
Purpose: To evaluate safety, feasibility and ecacy of FOLFOX in cancer
of the upper rectum (stages II and III, ≥12 cm) aer total (TME) vs. par-
tial (PME) mesorectal excision.
Methods: Upfront surgery was performed in 98 (median age: 69) partici-
pants of the GAST-05 phase II trial (ISRCTN35198481). Aer conrma-
tion of stage II or III (7th TNM/UICC-classication) 4 cycles of FOLFOX
(FA: 400 mg/m²; 5-FU: 2400 mg/m²; OX: 100 mg/m²) were indicated.
Acute and late toxicities were determined according NCI-CTCAE criteria
(v3.0). Survival was calculated using the logrank test, Kaplan-Meier esti-
mator, and multiparametric Cox proportional hazard regression models.
Results: Upfront surgery quality was good, moderate or poor quality
in 82.7, 16.3 and 1%, respectively. Advanced disease had to be stated in
>50%, due to pT4a/b (13.3%) or pN1/N2 status (42.9%). AdCTx was
started in 62 patients; 96.6% of planned cycles could be administered, and
5-FU and OX doses were 90.8% and 73.4% of target. During adCTx, 772
AEs were reported with hematologic (n=205), gastrointestinal (n=221)
and neurologic (n=151) AEs clustered; CTCAE-grade 3/4 occurred in
3.5%. During follow-up (median: 101 months), 386 late AEs were noted,
with 11.1% having grade 3/4. Neurotoxicity accounted for 24.4% (17.0%
grade 2) and diarrhea for 34.7% (18.4% grade 3/4). Together with fecal
incontinence (12.7%), 47.4% of all late events were due to defecation dis-
orders. Low anterior resection syndrome was present in 44.1% and more
frequent aer TME (p=0.007). Aer adCTx, the 3- and 5-year OS was
87.1% and 82.3%, respectively, vs. 75.0% and 68.8% (without adCTx).
Stage III patients had better DFS (p=0.058); 3- and 5-year DFS were
68.8% and 65.6%, respectively, vs. 40.0%. OS was also prolonged in stage
III (p=0.003); the 3- and 5-year OS was 81.3% and 78.1%, respectively
(vs. 40.0% without adCTx).
Discussion: is study contributes to the debate on optimal therapy for
upper rectal cancer. Stage II patients also appear to have a survival benet
with adCTx.
Conclusions: mFOLFOX improves survival in patients with stage III
upper rectal cancer.
Disclosure Statement: e authors declare no conict of interest.
1073
Preoperative chemoradiotherapy (preopCRT) for locally
advanced rectal cancer (LARC) - a benet for all? - the view
of a study site
Recca Talaulicar1; Andreas Leha2; Julie Schanz3; Johanna Kreutzer1;
Timotheus Ritter1; Tatiana Grammatikopoulou1; Torsten Liersch1
1Klinik für Allgemein-, Viszeral- und Kinderchirurgie, Universitätsmedizin
Göttingen, Göttingen, Deutschland
2Institut für Medizinische Statistik, Universitätsmedizin Göttingen, Göttingen,
Deutschland
3Klinik für Hämatologie und Medizinische Onkologie, Universitätsmedizin
Göttingen, Göttingen, Deutschland
Purpose: To evaluate ecacy of 5-FU-based preopCRT±OX followed by
total mesorectal excision and adjuvant CTx vs. upfront surgery for LARC
(<16 cm above anal verge).
Methods: 402 LARC patients (median age: 64 yrs) were treated between 1998
to 2013 in the CAO/ARO/AIO-94, -04 and GAST-05 (ISRCTN35198481)
trials. e ecacy of therapy was assessed by logrank test, Kaplan-Meier
estimator and univariable survival models. Multivariable proportional
Cox regression models were tted for risk factors and survival endpoints,
adjusting for risk factor, pretreatment, tumor location, and their 2-way
interactions, and treatment regimen.
Results: Aer upfront surgery (n=180), stages I to IV were diagnosed in
13.9, 40.0, 41.7, and 4.4%, respectively. Aer preopCRT (n=222), stages
0 to IV were detected in 14.9, 19.4, 33.6, 33.1, and 5.7%, respectively.
During 91m follow-up (median), 119 recurrences occurred in 30.0%;
local recurrences had been detected in 1% (alone) and 5.3% (together with
distant metastases). Paired contrast tests for OS showed that preopCRT
favored stages ≤II (HR: 0.37; p<0.001). Similarly, preopCRT showed a
positive eect for stages ≤II in the upper rectum (HR: 0.16; p = 0.004).
is eect appears to be synergistic, as OS was also better aer upfront
surgery in stages ≤II vs. >II (HR: 0.37; p = 0.018). For DFS, there was
a similar eect of preopCRT in favor of stages ≤II (HR: 0.37; p<0.001).
In CSS, preopCRT was in favor of stages ≤II (HR: 0.22; p<0.001) in the
lower and mid rectum and for carcinomas in the upper third (HR: 0.0096;
p=0.001). In this tumor location, patients with stages ≤II vs. >II per se
had better CSS (HR: 0.029; p = 0.007); thus, the actual benet of preop-
CRT remains questionable.
Discussion: In stage ≤II upper rectal cancer, there was no patient dis-
advantage when preopCRT was omitted. Whether patients with stage III
aer upfront surgery benet from more intensive adCTx (vs. FOLFOX)
should be assessed in clinical trials.
Conclusion: PreopCRT+OX resulted in better survival in stage ≤II cancer
(<12 cm above AV), and stages >II were identied as «non-responders».
Disclosure Statement: e authors declare no conict of interest.
1075
Peri-/postoperative quality control in locally advanced rectal
cancer (LARC) after preoperative multimodal treatment
(MMT) or upfront surgery– any evidence on survival?
Tatiana Grammatikopoulou1; Andreas Leha2; Julie Schanz3;
Johanna Kreutzer1; Laura Werle1; Charlotte de Boer1; Torsten Liersch1
1Klinik für Allgemein-, Viszeral- und Kinderchirurgie, Universitätsmedizin
Göttingen, Göttingen, Deutschland
2Institut für Medizinische Statistik, Universitätsmedizin Göttingen, Göttingen,
Deutschland
3Klinik für Hämatologie und Medizinische Onkologie, Universitätsmedizin
Göttingen, Göttingen, Deutschland
Purpose: To evaluate the role of peri-/postoperative control and clinico-
pathological risk factors in specimen aer total (TME) or partial (PME)
mesorectal excision in ≥stage II rectal cancer (≤16 cm above anal verge)
treated with preoperative, 5-FU-based chemoradiotherapy (preop-
CRT)±Oxaliplatin (OX) or upfront surgery.
Methods: 402 participants of the CAO/ARO/AIO-94, -04 and GAST-05
(ISRCTN35198481) trials with stage ≥II rectal cancer were included in
this project at a single study site. Standardized peri-/postoperative qual-
ity control of the specimen and extended histopathological work-up was
performed according to trial protocols, MERCURY criteria, and the 7th
TNM-/UICC-classication. e impact of selected prognostic parameters
on survival was investigated by using Logrank test, Kaplan-Meier estima-
tor, uni-/multiparametric Cox proportional hazard regression models,
and interaction eects testing models.
Results: Optimal quality of TME/PME-surgery was demonstrated peri-
and postoperatively in 80.4% and 78.7% of specimen, respectively. e
rate of optimal resections aer preopCRT+OX was increased to 82.5%
and 77.8%, respectively, compared with 76.6% and 70.3% for MMT with-
out OX. In patients with LARC in the lower rectum (<12 cm) treated
with preopCRT who had positive pCRM status, there was a benet in DFS
(HR: 5.9; adjusted p=0.002). Aer preopCRT, negative nodal status (N0)
showed better DFS for LARC in the lower and mid thirds of the rectum
(ypN0 status; HR: 0.41, p<0.001) and in the upper third aer upfront sur-
gery (pN0 status; HR: 0.44; p=0.003) and aer preopCRT (ypN0 status;
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 77
HR: 0.25, p=0.003). Further data from multivariable survival models will
be presented at DKK 2022.
Discussion: Standardized peri/postoperative control of rectal cancer
surgery provides signicant improvement in specimen quality and more
accurate cancer staging.
Conclusion: Based on high-quality surgery, preoperative CRT synergisti-
cally improves survival in intermediate and lower rectal cancer (<12 cm)
and opens the door for risk-adapted adjuvant treatment.
Disclosure Statement: e authors declare no conict of interest.
1077
MRI (1.5T) monitoring as early predictor of survival in
advanced rectal cancer during preoperative multimodal
treatment (MMT)
Torsten Liersch1,1; Ali Seif Amir Hosseini2; Timotheus Ritter1;
Carsten-Olive Sahlmann3; Johanna Kreutzer1; Leif Hendrik Dröge4;
Julia Kitz5; Andreas Leha6
1Klinik für Allgemein-, Viszeral- und Kinderchirurgie, Universitätsmedizin Göttingen;
Göttingen, Deutschland
2Institut für Diagnostische und Interventionelle Radiologie, Universitätsmedizin
Göttingen, Göttingen, Deutschland
3Klinik für Nuklearmedizin, Universitätsmedizin Göttingen, Göttingen, Deutschland;
4Klinik für Strahlentherapie und Radioonkologie, Universitätsmedizin Göttingen,
Göttingen, Deutschland
5Institut für Pathologie, Universitätsmedizin Göttingen, Göttingen, Deutschland
6Institut für Medizinische Statistik, Universitätsmedizin Göttingen, Göttingen,
Deutschland
Background: Baseline 1.5 Tesla MRI (MRI-I) is standard for locally
advanced rectal cancer (LARC) to indicate preoperative 5-FU-based
chemoradiotherapy (preopCRT). e prognostic signicance of pre-sur-
gical MRI-II (in dierence (Δ) to MRI-I) is controversial.
Methods: In this monocentric posthoc-study, 125 patients (47 f, 78 m;
median age: 68 years) with LARC (clinical stages II to IV in 5.6%, 92.0%,
and 2.4%, respectively) received preopCRT ± Oxaliplatin followed by
TME-surgery. Imaging and post-surgical parameters were tested for asso-
ciation with recurrence-free (RFS), overall (OS) and cancer-specic (CSS)
survival. ree multiple Cox regression models were built using grouped
lasso penalization: (1) pre-surgical (imaging), (2) post-surgical (patholog-
ical) and (3) post-treatment (all variables). Patients were classied in high-
or low-risk survivors in a 10-fold cross validation (CV). e post-surgical
models were extended with additionally informative imaging parameters
as conrmed by likelihood ratio tests.
Results: Post-surgical staging revealed (yp)stages 0 to IV in 13.6%, 28.0%,
25.6%, 23.2% and 9.6%, respectively. Restricted mean for RFS, OS and
CSS were 88.9±5.5, 100.4±4.9 and 119.4±4.7 months. Survival rates
aer 2.5, 5 and 7.5 years amounted to 68.8%, 59.9%, 56.4% for RFS; to
84.8%, 68.7%, 60.3% for OS, and to 89%, 80% and 73% for CSS, respec-
tively. In the pre-surgical models increased hazard ratios (HR) for RFS
were observed in MRI-I_Δ_MRI-II T status (p=0.01) and MRI-I_Δ_
MRI-II TE (longitudinal tumor extent) (p=0.04). Increased HR for OS
was seen in MRI-I_Δ_MRI-II TE (p=0.02). CV of the pre-surgical risk
models dierentiated survivors in RFS (p=0.019) and OS (p<0.001).
Discussion: MRI monitoring is useful for early prediction of survival in
advanced rectal cancer
Conclusion: Our ndings strongly suggest MRI as easily available
pre-surgical tool for early adjustment of (multimodal) treatment.
Disclosure Statement: e authors declare no conict of interest.
Gastrointestinal (Non-colorectal) Cancer
Best-of-Abstract-Vortrag
1005
Real-World Use of PARP inhibitors in BRCA1/2-Mutated
Pancreatic Cancer: A Retrospective Analysis
Danmei Zhang1; Suvina Amin2; Weiyan LI2; Seongjung Joo3;
Gboyega Adeboyeje3; Patricia Dearbeloa4; Emanuel F Petricoin III4,5;
Edik M Blais4; Michael J Pishvaian4,6
1Klinikum Großhadern, Medizinische Klinik und Poliklinik III, München,
Deutschland
2AstraZeneca, Gaithersburg, USA
3Merck, Kenilworth, USA
4Perthera Inc., Holliston, MA , USA
5George Mason University, Fairfax, USA
6Johns Hopkins School of Medicine, Baltimore, USA
Background: Olaparib is the only PARP inhibitor (PARPi) approved in the
EU and the US as maintenance treatment for biomarker-selected patients
with mPaC in the 1st line platinum-sensitive setting. However, treatment
sequencing can be heterogeneous, and there is a lack of real-world data on
patterns of PARPi use in relation to platinum use in BRCA1/2-mutated
mPaC.
Methods: Longitudinal records collected between 1/2012-12/2020 were
analyzed for a cohort of 55 mPaC patients with BRCA1 or BRCA2 muta-
tions identied by commercial NGS testing who enrolled in Pertheras
US real-world observational registry study. Treatment patterns including
PARPi utilization and platinum-sensitivity (16 weeks without progression
at any point within known history) were abstracted via physician notes
across all lines of therapy.
Result: PARPi use was documented in 60% (N=33) of 55 patients with
BRCA1/2-mutated mPaC in any treatment setting. Within this cohort,
21 patients received a single agent PARPi outside of clinical trials.
Among these patients, only 38% (8 of 21) transitioned to a PARPi in a
platinum-sensitive context, and only 14% (3 of 21) of these transitions
occurred before 2nd line. Notably, 6 patients received a PARPi in the plat-
inum-resistant setting. Within the broader cohort, platinum-sensitive
criteria was fully met for 73% (40 of 55); however, only 49% (27 of 55)
reached this milestone of platinum-sensitivity prior to initiating a 2nd line
therapy.
Conclusion: e majority of these BRCA1/2-mutated patients received
a PARPi-based therapy in a variety of contexts with respect to line of
therapy and prior platinum history. ese ndings highlight the value of
upfront genetic and molecular testing and the need for further exploration
to identify factors associated with treatment response as well as optimized
treatment sequencing.
Indication of source:
1 American Society of Clinical Oncology Gastrointestinal Cancer Symposium,
Jan 20-22, 2022
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organiser KUKM GmbH and KUKM
can disclose them if needed.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts78
Poster
10
Distance matters: Correlation of HCC nodule distance to
overall survival
Yuquan Qian1; Baojiang Liu2; Christel Weiss3; Xu Zhu2; Andreas Teufel1,4,5
1Heidelberg University, Medical Faculty Mannheim, University Medical Center
Mannheim, Department of Medicine II, Mannheim, Deutschland
2Peking University Cancer Hospital and Institute, Key Laboratory of
Carcinogenesis and Translational Research (Ministry of Education), Department
of Interventional Therapy, Beijing, China, VR
3Heidelberg University, Medical Faculty Mannheim, Heinrich Lanz Center for
Digital Health, Department of Statistics, Biomathematics and Information
Processing, Mannheim, Deutschland
4Heidelberg University, Medical Faculty Mannheim, University Medical Center
Mannheim, Department of Medicine II, Division of Hepatology, Division of
Bioinformatics, Mannheim, Deutschland
5Heidelberg University, Medical Faculty Mannheim, Center for Preventive
Medicine and Digital Health Baden-Württemberg (CPDBW), Clinical Cooperation
Unit Healthy Metabolism, Mannheim, Deutschland
Background: Hepatocellular carcinoma (HCC) may occur with several
simultaneous tumor foci in the liver (multifocal HCC). Molecular biol-
ogy indicated that the larger the distance between two tumor nodules, the
more those two nodules diered in their genetic composition. erefore,
we explored whether the overall survival of patients with HCC depends
on the mutual distance of the HCC nodules.
Methods: In a retrospective study of 92 patients, CT/MRI images and sur-
vival data of the patients were collected. Based on the CT or MRI images
at the time of diagnosis, the size of each tumor, the distance between the
centers (center distance) and adjacent edges (edge distance) of the tumor
nodules were measured respectively. ese data, combined with the num-
ber of tumor nodules and clinical characteristics, were compared with the
patients overall survival data.
Result: As expected, the average tumor diameter was signicantly associ-
ated with patient survival in univariate cox regression analysis (p=0.00028,
HR=1.2). However, in multivariate analysis, the average center distance
(p=0.036, HR=1.18) and average edge distance (p=0.033, HR=0.84) were
also signicantly associated with survival.
Discussion: Our data provided new insight into assessing the survival of
multifocal HCC patients. We showed that the distance between tumor
nodules is a potential predictor of the overall survival of patients with
multifocal HCC, which may be due to the fact that distance is related to
rapid biological evolution and multiple molecular alterations.
Conclusion: Not only the size of multiple HCC lesions but also their dis-
tance is important for the prognosis of patients with HCC. is may be of
particular interest in patients with two nodules and BCLC B and C stages
for the selection of therapeutic modalities and/or procedures.
Indication of source (Optional, bitte löschen Sie diesen Absatz, wenn Sie
keine Quellenangaben haben):
Indication of source:
1 is project was also submitted to e Liver Meeting 2021
Disclosure Statement: e authors declare the following: Prof. Teufel is supervisor
of Yuquan Qian for doctoral study.
32
IMbrave150: exploratory ecacy and safety results of
atezolizumab + bevacizumab vs sorafenib in patients (pts)
with unresectable hepatocellular carcinoma (HCC) who had
prior locoregional therapy (LRT)
Peter R. Galle1; Riad Salem2; Richard S. Finn3; Michel Ducreux4;
Amit G. Singal5; Alan Nicholas6; Sairy Hernandez6; Wendy Verret6;
Philippe Merle7; Andrew X. Zhu8,9
1I. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz, Mainz,
Deutschland
2Northwestern University, Chicago, USA
3Jonsson Comprehensive Cancer Center, Geen School of Medicine at UCLA, Los
Angeles, , Los Angeles, USA
4Gustave Roussy Cancer Center, Villejuif, Frankreich
5UT Southwestern Medical Center, Dallas, USA
6Genentech Inc., South San Francisco, USA
7University Hospital La Croix-Rousse, Lyon, Frankreich
8Massachusetts General Hospital Cancer Center, Harvard Medical School,
Boston, USA
9Jiahui International Cancer Center, Shanghai, China, VR
Background: Atezolizumab (atezo) + bevacizumab (bev) has been
approved in > 70 countries for systemic treatment (tx)–naive pts with
unresectable HCC, based on IMbrave150 (NCT03434379¸ Finn RS
NEJM 2020). Here, we report post hoc exploratory results of atezo + bev
vs sorafenib (sor) in pts who had prior LRT using updated data with 12
months of further follow-up from primary analysis.
Methods: Pts were randomised 2:1 to atezo 1200 mg IV q3w + bev 15 mg/
kg IV q3w or sor 400 mg bid until unacceptable toxicity or loss of clinical
benet per investigator. IMbrave150 enrolled 501 systemic tx–naive pts
with unresectable HCC, ≥ 1 measurable untreated lesion (RECIST 1.1),
Child-Pugh class A liver function and ECOG PS ≤1, including pts with
prior LRT.
Result: 175, 84, 77 atezo + bev and 80, 44, 41 sor pts had 0, 1-2 and ≥ 3
prior lines of LRT, respectively. Compared with sor, atezo + bev pts had
median overall survival (mOS) of 19.4 vs 13.1 mo (HR, 0.61; 95% CI: 0.44,
0.86) in pts without prior LRT, 22.8 vs 10.2 mo (HR, 0.60; 95% CI: 0.36,
1.00) in pts with 1-2 LRTs and 17.4 vs 16.6 mo (HR, 0.83; 95% CI: 0.51,
1.37) in pts with ≥ 3 LRTs.
In the three LRT-subgroups (0, 1-2, ≥ 3 prior lines), median progres-
sion-free survival in atezo + bev pts was 6.7 / 9.4 / 6.7 months, vs 4.8 /
4.0 / 4.4 months in sor pts. e objective response rates were 29 / 35 / 25
% in the atezo + bev subgroups, and 15 / 5 / 10 % in the sor subgroups. A
complete response occurred in 5 %, 14 % and 8 % in atezo + bev pts, but in
only one of 159 evaluable sor pts. Stable disease was documented in 39-49
% in the atezo + bev subgroups, and in 37-53% in sor pts.
Grade 3-4 treatment-related adverse events were seen in 79 (46%), 33
(39%) and 31 (41%) atezo + bev pts and 30 (39%), 20 (49%) and 22 (58%)
sor pts who had 0, 1-2 and ≥ 3 LRTs, respectively.
Conclusion: Survival benet with Atezolizumab + Bevacizumab over
Sorafenib was seen in patients regardless of the number of prior LRTs.
Atezolizumab + Bevacizumab seemed to have more benet in patients
with 1-2 vs ≥ 3 prior LRTs, suggesting an optimal time for switching from
LRT to systemic therapy.
Disclosure Statement: e authors declare the following: Honoraria -
Adaptimmune; Bayer Schering Pharma; Bristol-Myers Squibb; Ipsen; Lilly; MSD;
Roche/Genentech; Sirtex Medical Consulting or Advisory Role - Adaptimmune;
Bayer Schering Pharma; Bristol-Myers Squibb; Lilly; MSD; Roche/Genentech;
Sirtex Medical Speakers’ Bureau - Bayer Schering Pharma; Ipsen; Lilly; Roche
Travel, Accommodations, Expenses- Bayer Schering Pharma; Lilly; Sirtex Medical
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 79
40
N-CROSS neoadjuvant chemoradiotherapy of the esophageal
cancer at the Nuremberg Hospital North
Thomas Gryc1; Christian Grehn1; Irina Bosancu1; Cansu Cabuk1;
Martin Wilhelm2; Marcus Seifert2; Attila Dubecz3; Wolfgang Brückl2;
Hubert Stein3; Clemens Albrecht1
1Nürnberg, Praxis für Strahlentherapie Nordstrahl, Nürnberg, Deutschland
2Paracelsus Medizinische Privatuniversität , Klinikum Nürnberg, Innere Medizin,
Nürnberg, Deutschland
3Paracelsus Medizinische Privatuniversität, Klinikum Nürnberg, Chirurgie,
Nürnberg, Deutschland
Background: We conducted an assessment of eectivity for our multi-
modal treatment schedule of loco regionally advanced esophageal cancer.
Methods: Patientdata treated for locally advanced esophageal cancer or
cancer of the gastroesophageal junction between 01/2015 and 09/2020
was analyzed. Patients were treated in analogy to the CROSS-protocol.
Alternatively, a chemoradiotherapy (RCT) with simultaneous 5-uo-
rouacil with a platinum compound was applied. Aer an interval of 2.1
months, surgery including a two-eld lymphadenectomy was performed.
Results: Of the 49 patients evaluated, 83.7 % were male. Histological
workup revealed 61.2 % adenocarcinoma (AC) and 38.2 % squamous
cell carcinoma (SCC). 33.3 % of the SCC tumors and 27.8 % of the AC
received a treatment in analogy to the CROSS- protocol and the remain-
ing received a RCT of 45 Gy and 5-uorouacil/platinum. A pathological
complete remission was achieved in 26.5 % and in additional 36.7% less
than 10% vital tumor cells were detected in the tumor bed aer neoad-
juvant treatment (Becker tumor regression grade IB). us, neoadjuvant
RCT resulted in grade I regression in a total of 63.2%. R0 resection was
achieved in 100% of the patients. 2-year overall survival was 80% inde-
pendently of tumor histology (p=0.325) or the neoadjuvant treatment
(p=0.923). Median disease free survival (DFS) was 7.3 months and was
shorter for AC than for SCC (p=0.021). In case of a pathologic response
>90% the disease free survival was signicantly improved to 12.8 months
(p=0.034). For SCC tumors treated with CROSS, DFS was prolonged. Still,
in general DFS did not dier between CROSS-protocol and the 5-uo-
rouacil/platinum based therapy (p=0.436).
Conclusion: Our data demonstrate the good feasibility of multimodal
therapeutic regimen in clinical routine in the context of close interdis-
ciplinary collaboration. Emphasis should be paid to individual adapta-
tion of the therapy regimen to the tumor specications. In particular, the
degree of pathologic response to neoadjuvant treatment exerts a signi-
cant inuence on clinical outcome.
Disclosure Statement: e authors declare no conict of interest.
59
Long-term survival of a patient with metastatic and recurrent
pancreatic acinar cell carcinoma harboring somatic BRCA1/2
variants of unknown signicance treated with Olaparib
maintenance therapy following local treatment
Christian Müller1; Sabine Franke2; Maciej Janusz Powerski3;
Thomas Brunner4; Marino Venerito1
1Universitätsklinik für Gastroenterologie, Hepatologie und Infektiologie,
Otto-von-Guericke Universitätsklinikum, Magdeburg, Deutschland
2Institut für Pathologie, Otto-von-Guericke Universitätsklinikum, Magdeburg,
Deutschland
3Universitätsklinik für Radiologie und Nuklearmedizin, Otto-von-Guericke
Universitätsklinikum, Magdeburg, Deutschland
4Universitätsklinik für Strahlentherapie, Otto-von-Guericke Universitätsklinikum,
Magdeburg, Deutschland
Background: Acinar cell carcinoma of the pancreas (PACC) is a rare
malignant disease oen with an advanced or metastatic stage at initial
diagnosis. ere are no standardized therapy recommendations for the
treatment of non-resectable disease.
Methods: Here we present a case of a patient with a PACC who has shown
a sustained response to multimodal therapy (chemotherapy, local treat-
ment and targeted therapy).
Result: In 2017, a 61-year-old man presented with persistent back pain.
Initial imaging revealed a hypodense lesion in the pancreatic corpus and
both lobes of the liver. Histological examination of a hepatic lesion con-
rmed the diagnosis of PACC. He received a 12 cycles FOLFIRINOX
achieving partial remission, followed by FOLFIRI maintenance therapy
(15 cycles). Aer 22 months, a progressive disease was documented.
Gemcitabine/nab-paclitaxel failed to stop progression. us, the patient
received Stereotactic Body Radiation erapy of the primary tumor and
transarterial radioembolisation of the liver metastases. e mutation anal-
ysis of the tumor biopsy revealed mutations with unknown signicance
in both BRCA1 (c.800C>T) and BRCA2 (c224C>T). Maintenance treat-
ment with the PARP inhibitor Olaparib induced disease control over 12
months, despite an early dose reduction due to neutropenia and thrombo-
cytopenia. ereaer, a documented progression of liver metastases was
controlled with transarterial chemoembolization. Olaparib maintenance
therapy was kept until disease progression in April 2022. Overall, with this
approach the patient is still alive aer 61 months.
Discussion: In our patient, Olaparib maintenance therapy may have
contributed to disease control aer local treatment. Further studies are
needed to conrm a pathogenic role for the BRCA1 c.800C>T and BRCA2
c224C>T somatic variants.
Conclusion: In our patient with a chemo-resistant PACC, harboring
somatic BRCA1/2 variants of unknown signicance, Olaparib mainte-
nance therapy following local ablative procedures was feasible and con-
tributed to an excellent survival benet.
Disclosure Statement: e authors declare no conict of interest.
179
Inuence of the hepatic microenvironment on the migration
behavior of premalignant and malignant pancreatic ductal
epithelial cells
Svenja Quaester1, Silje Beckinger1, Tina Daunke1, Lisa-Marie Philipp1,
Claudia Seemann1, Sascha Rahn2, Susanne Sebens1
1Institut für Experimentelle Tumorforschung, Christian-Albrechts-Universität zu
Kiel, Kiel, Deutschland
2Institute of Biochemistry, Christian-Albrechts-Universität zu Kiel, Kiel,
Deutschland
Background: e poor prognosis of patients with pancreatic ductal ade-
nocarcinoma is ascribed to diagnosis in advanced stages, pronounced
therapy resistance and high recurrence rates, the latter oen associated
with liver metastases. In order to develop eective therapeutic options,
a better understanding of the underlying processes of metastasis and the
involved Epithelial-Mesenchymal-Transition (EMT) is essential. us, the
present study investigated the impact of the hepatic microenvironment on
EMT and migration behavior of pancreatic ductal epithelial cells (PDEC).
Methods: Premalignant (H6c7-Kras) and malignant (PancTu1) PDEC
were indirectly cocultured with hepatic stellate cells (HSC) or hepatic
myobroblasts (HMF), mimicking a physiological or inamed hepatic
microenvironment. Aer 5 days, PDEC proliferation was assessed by cell
counting, EMT gene and protein expression were analyzed via PCR and
Western Blot and migration was examined performing wound healing
assays.
Result: Both proliferation rates and expression of EMT inducing fac-
tors were increased in PDEC by coculture with HMF compared to HSC.
Accordingly, E-cadherin expression was higher in both PDEC lines under
HSC compared to HMF coculture, with PancTu1 cells showing higher
basal expression levels than H6c7-Kras cells. In line, H6c7-Kras cells
migrated faster than PancTu1 cells, however, HSC coculture led to faster
wound closure compared to HMF coculture, in both cell lines.
Discussion: Overall these data suggest that a physiological hepatic
microenvironment reduces proliferation and E-cadherin expression
but supports migratory abilities in PDEC. In contrast, an inamed liver
micromilieu promotes a PDEC phenotype characterized by enhanced
proliferation and E-Cadherin expression but reduced cell migration.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts80
Conclusion: e hepatic microenvironment impacts cell proliferation
and EMT associated properties in premalignant and malignant PDEC in
dependence on the inammatory status.
Disclosure Statement: e authors declare no conict of interest.
211
First results from the prospective national intersectoral cohort
study JADE to assess characteristics, treatment and outcome
of patients with hepatocellular or cholangiocellular carcinoma
In Germany
Robert Thimme1; Jan Schröder2; Jens Uhlig3; Jens Freiberg-Richter4;
Matthias Zingerle5; Anke Schlenska-Lange6; Christiane Hering-Schubert7;
Fee Bengsch8; Larissa Elisabeth Hillebrand8; Hans Ulrich Siebenbach8;
Martina Jänicke8; Wolf Peter Hofmann9; Philippe Pereira10; Thomas Berg11;
Peter Galle12
1Universitätsklinikum Freiburg, Freiburg i. Br., Deutschland
2Praxis für Hämatologie, Onkologie, Palliativmedizin, Mülheim an der Ruhr,
3Onkologie Muldental, Naunhof
4BAG / Onkologische Gemeinschaftspraxis, Dresden, Deutschland
5Hämato-Onkologische Überörtliche Gemeinschaftspraxis Pasing und
Fürstenfeldbruck, München, Deutschland
6Krankenhaus Barmherzige Brüder, Regensburg
7St. Georg Klinikum, Eisenach, Deutschland
8iOMEDICO, Freiburg i. Br., Deutschland
9MVZ für Gastroenterologie am Bayerischen Platz, Berlin, Deutschland
10SLK-Kliniken , Heilbronn, Deutschland
11Universitätsklinikum Leipzig, Leipzig, Deutschland
12Universitätsmedizin Mainz, Mainz, Deutschland
Background: Hepatocellular carcinoma (HCC) and intrahepatic
cholangiocarcinoma (iCC) are the most common types of primary liver
cancer. Prospective real-world evidence of patients (pts) with liver cancer,
however, is still scarce.
Methods: JADE is a prospective, multicenter, intersectoral, longitudinal
cohort study that will collect data of up to 1,000 pts with HCC or CCC
from approximately 100 sites (clinics and oce-based) in Germany. Since
August 2020, pts with early, intermediate or advanced/metastatic stage
HCC or CCC are enrolled at start of local or systemic treatment. Data
are collected in electronic case report forms. Pts and tumor characteris-
tics, treatment and clinical and patient-reported outcome data are docu-
mented. In addition, pts can consent to the use of their routinely collected
tumor samples in future translational research.
JADE (NCT04510740) was approved by local ethics.
Result: At rst annual data base cut (2021-APR-30), 167 pts had been
recruited at 55 sites. Here, rst results are presented for pts with advanced
disease. Updated results (data base cut 2022-APR-30) will be shown at
the congress.
e 21 pts with advanced HCC (71% male) had a median age of 71 years,
81% had comorbidities and most pts were in rather impaired overall
condition (ECOG 0: 38%). e most frequently used 1L treatments were
atezolizumab+bevacizumab (n=13, 65%), and lenvatinib (n=4, 20%).
e 38 pts with advanced CCC (56% male) had a median age of 70 years,
84% had comorbidities and most pts were in quite fair condition (ECOG
0: 50%). In most pts (n=35), gemcitabine was applied in 1L treatment
(most frequently as gemcitabine+cisplatin (n=31, 82%).
Conclusion: JADE will, for the rst time, present real-world data on pts
and tumor characteristics, treatment and outcomes of pts with liver and
biliary tract cancer across all health care sectors in Germany. In the future,
JADE will shed light on the treatment landscape in real-world and will
help to identify unmet medical needs for future clinical research.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organiser KUKM GmbH and KUKM
can disclose them if needed.
259
Outcomes of patients with locally advanced or metastatic
pancreatic cancer treated with dierent sequential treatment
strategies –data from the prospective Tumour Registry
Pancreatic Cancer
Susanna Hegewisch-Becker1; Marcel Reiser2; Steen Dörfel3;
Christian Lerchenmüller4; Hartmut Linde5; Thomas Wolf6;
AdrianBinninger7; Natalie Wetzel7; Martina Jänicke7; Norbert Marschner8
1Hämatologisch-Onkologische Praxis Eppendorf (HOPE), Hamburg, Deutschland
2PIOH - Praxis Internistische Onkologie und Hämatologie, Köln, Deutschland
3Onkozentrum Dresden/Freiberg, Dresden, Deutschland
4Hämatologisch-onkologische Gemeinschaftspraxis, Münster, Deutschland
5MVZ für Blut- und Krebserkrankungen, Potsdam, Deutschland
6BAG / Onkologische Gemeinschaftspraxis, Dresden, Deutschland
7iOMEDICO, Freiburg i.Br., Deutschland
8Praxis für Interdisziplinäre Onkologie & Hämatologie, Freiburg i.Br., Deutschland
Background: FOLFIRINOX (FFX) and gemcitabine (GEM) + nab-pacl-
itaxel (GnP) are the two most active 1st-line treatment (1L) options and
standard of care for patients (pts) with locally advanced or metastatic
pancreatic cancer (mPC) and good performance status. Intense eorts are
ongoing to establish an optimized sequential treatment strategy that oers
improved survival but clinical trials on sequential treatments are miss-
ing. e clinical registry TPK provides detailed insight into longitudinal
treatment data and outcomes of pts with mPC treated in routine clinical
practice in Germany.
Methods: TPK is a prospective, multicenter, cohort study of pts with mPC
receiving systemic therapy. Since 2014, >2000 pts from 120 sites across
Germany were registered prior to start of 1L. Detailed data on patient
and tumor characteristics, treatment and outcome are recorded. Herein,
outcomes based on treatment sequences were evaluated. Progression-free
survival 2 (PFS2) was dened as time from start of 1L until rst progres-
sion aer start of 2nd-line (2L) treatment or death from any cause.
Result: Between 2014 and 2021, a total of 482 pts with mPC received
at least two lines of treatment. ereof, 228 pts received FFX>GnP, 101
pts GnP>FOLFOX/OFF, 74 pts GnP>nal-IRI+5-FU (NALIRI) and
44 pts FFX>GEM. Since approval of NALIRI in 2016, the sequence
GnP>NALIRI (15%) has become the second most common sequential
treatment. Median age for pts receiving FFX in the 1L was 61-62 years, for
pts receiving GnP in their 1L median age was 70 years. Median PFS2 for
all sequences was 9-11 months, median OS was 12-13 months. Updated
data will be presented.
Conclusion: e choice of treatment sequence for pts with mPC is highly
age-dependent. Patients starting with FFX are younger. However, outcome
data on PFS2 and OS are comparable in all those pts. who are t enough
to receive a 2L treatment following either FFX or GnP as 1L. Upcoming
analyses from the TPK are planned for conrmation of these results with
matched cohorts and integration of data on patient reported outcomes
such as health-related quality of life.
Disclosure Statement: e authors declare that there are conicts of interest.
econnections were submitted to the congress organiser KUKM GmbH and
KUKM can disclose them if needed.
293
Regulation of Macrophage-Recruitment in a Pancreatic
Cancer Model - Comparison of the Kampo-Medicine
Juzen-taiho-to with Gemcitabine
Paulina Siebel1; Joanna Napp1,2; Volker Ellenrieder1; Silke Cameron1
1Department of Gastroenterology, Gastrointestinal Oncology and
Endocrinology, University Medical Center Göttingen (UMG)
2Max-Planck Institute of Experimental Medicine, Göttingen
Background: Pancreatic ductal adenocarcinoma (PDAC) has a poor
prognosis. A better understanding of molecular mechanisms opens new
therapeutic methods. Japanese traditional herbal medicine (Kampo-
medicine) is immune-modulatory, improves general fatigue and side-
eects of chemotherapy.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 81
Methods: An orthotopic transplantation model of KPC cells into the
pancreas of C57BL/6 mice was established. Mice were treated with
Gemcitabine (Gem, n=12), Juzen-taiho-to (Juz, a standardized Japanese
herbal medicine, n=17), the combination (Gem+Juz, n=17), or NaCl (ctrl,
n=12). Aer sacrice, IHC (CD68, CD45) was performed for macrophage
(MΦ)/ lymphocyte inltration. Immune-modulation, chemokine release
of tumor cells (KPC) and cytokine expression of MΦ (MH-S) were stud-
ied by Western Blot, Realtime PCR and Cytokine Chemokine Array.
Result: Combination treatment prolonged survival. An increase of CD68+
MΦ was observed in Gem+Juz, compared to ctrl (p<0.001). No elevation
was seen for CD206+ M2-MΦ. e number of tumor-associated CD45+
cells did not change. With Juz or Gem+Juz treatment, KPC-cells released
more MΦ-chemoattractant cytokines (i.e. CCL2, CCL20, CXCL2) com-
pared to ctrl or Gem. Juz or Gem+Juz treated MΦ secreted more M1 cyto-
kines (i.e. IL6, TNFa, CXCL10) than ctrl or Gem alone.
Discussion: PDAC cells recruit and polarize MΦ into tumor associated
MΦ (TAM). It is known that TAMs release deoxycytidine (dC), a pyrim-
idine analog, involved in DNA synthesis. Gem is a modied pyrimidine
analog and thus prevents DNA synthesis. Both are taken up by tumor
cells. Based on their molecular similarity, dC competes with Gem for
DNA synthesis/breakdown and thus reduces the therapeutic ecacy
of Gem. We propose that whilst Juz increases M1-MΦ, Gem has more
anti-tumor ecacy.
Conclusion: PDAC-mice live longer with combination therapy. We sug-
gest that this is due to an enhanced cytotoxicity through an increased
number of M1- MΦ enhancing Gem ecacy. To understand the molecu-
lar mechanisms and anti-tumorigenic eect of Juz / chemotherapy treat-
ment, further research is necessary.
Disclosure Statement: e authors declare no conict of interest.
335
Global Expanded Access Program (EAP) to pemigatinib
for patients (pts) with previously treated locally advanced
or metastatic cholangiocarcinoma (CCA) and FGFR2 fusions
or rearrangements
Anouk Lindley1; Gerald Prager2; Michael Bitzer3; Timothy C. Burn1;
Christine F. Lihou1; Elisabeth Croft Richards1
1Incyte Corporation, Wilmington, USA
2Medical University of Vienna, Vienna, Österreich
3Medizinische Universitätsklinik Tübingen, Tübingen, Deutschland
Background: e global pemigatinib (PEMI; INCB054828) EAP was
conducted to make PEMI available to individual pts who, in the opin-
ion and clinical judgment of the treating physician, would benet from
receiving PEMI for the treatment of locally advanced or metastatic CCA
and cannot be treated satisfactorily with an authorized medicinal product.
Methods: Eligible pts were aged ≥18 years with previously treated CCA
and FGFR2 fusions/rearrangements, and with documented disease pro-
gression/intolerance aer ≥1 line of prior systemic therapy. Pts received
oral PEMI 13.5 mg QD until dose reduction, discontinuation or EAP
completion following local approval and access. Data collected were
demographics, duration of therapy, dosing and discontinuations, FGFR2
testing/status, and safety. Various testing platforms were allowed for
assessment of FGFR2 status.
Result: A total of 79 pts received PEMI from 68 physicians through the
EAP from January 2020 to June 2021 (Europe, 86.1%; Canada, 8.9%; USA,
3.8%; Israel, 1.3%; median age, 61 years [IQR, 48–67]; women, 67.1%;
≥1 reported prior therapy, 89.9%, most commonly cisplatin-gemcitabine
[41.8%] and FOLFIRI [8.9%]). Median duration of treatment was 102 days
(IQR, 45–189), with several pts remaining on PEMI at data cut o. Of the
79 pts receiving PEMI 13.5 mg QD, 11 (13.9%) reduced dose (9 mg QD,
n=8; 4.5 mg QD, n=1; unspecied, n=2) due to AEs; 9 (11.4%) pts discon-
tinued due to AEs. Pts were most commonly tested for FGFR alterations
using local assay (38.0%), FoundationOneTM (36.7%), or ermoFisher
OncomineTM (17.7%) platforms. Among all 79 treated pts, 50 (63.3%)
experienced all cause AEs, most commonly hyperphosphatemia (25.3%);
23 (29.1%) experienced serious AEs, most commonly disease progression
(3.8%), death (3.8%), or hypercalcemia (2.5%).
Discussion: In a real-world setting, PEMI safety was consistent with its
known AE prole in previously treated pts with CCA and FGFR2 fusions/
rearrangements.
Conclusion: e results indicate that pts with CCA should receive molec-
ular testing to identify eligible pts who might benet from PEMI.
Disclosure Statement: e authors declare the following: Gerald Prager served as
a consultant and on symposiums for Merck Serono, BMS, Roche, Amgen, Sano,
Lilly, Servier, Taiho, Bayer, Halozyme, MSD, Celgene, Incyte, and Terumo; Michael
Bitzer served as a consultant and on symposiums for Roche Pharma, Incyte,
MSD, BMS, and Bayer; Anouk Lindley, Timothy C. Burn, Christine F. Lihou, and
Elisabeth Cro Richards each hold Incyte stock and were employees at Incyte at
time work was done.
344
Identication of a prognostic systemic inammation
score (SIS) in patients (pts) with advanced intrahepatic
cholangiocarcinoma (iCCA) treated with palliative
chemotherapy (CTX)
Marlene Maßmann1; Andreas Paul2; Peter Markus3; Brigitte Schumacher4;
David Albers4; Saskia Ting5; Bastian Mende6; Julius Röhrle1;
Isabel Virchow1; Vivian Katrin Rosery1; Katharina Laue1; Gregor Zaun1;
Karina Kostbade1; Michael Pogorzelski1; Kurt Werner Schmid5;
Jens Siveke1; Hans-Ulrich Schildhaus5; Martin Schuler1; Marcel Wiesweg1;
Stefan Kasper-Virchow1
1Universitätsklinikum Essen, Westdeutsches Tumorzentrum , Innere Klinik
(Tumorforschung), Essen, Deutschland
2Universitätsklinikum Essen, Klinik für Allgemein-, Viszeral- und
Transplantationschirurgie, Essen, Deutschland
3Elisabeth-Krankenhaus Essen, Klinik für Allgemein-, Viszeral- und
Unfallchirurgie, Essen, Deutschland
4Elisabeth-Krankenhaus Essen, Klinik für Innere Medizin und Gastroenterologie,
Essen, Deutschland
5Universitätsklinikum Essen, Institut für Pathologie, Essen, Deutschland
6Universitätsklinikum Essen, Zentral Apotheke, Essen, Deutschland
Background: Systemic inammatory response parameters (SIR) are
known prognostic markers in dierent tumour entities but have not been
evaluated in pts with iCCA.
Methods: SIR markers were retrospectively evaluated in 219 pts with
iCCA treated with systemic CTX at the West German Cancer Center
Essen. e SIR markers: neutrophile/lymphocyte ratio (NLR), lympho-
cyte/monocyte ratio (LMR), CRP and the modied Glasgow Prognostic
Score (mGPS) were correlated with clinico-pathological ndings,
response to CTX (ORR), progression-free (PFS) and overall survival (OS)
using Kaplan-Meier curves, univariate and multivariate Cox proportional
models.
Results: Median overall survival (OS) of the study population was 17.3
months (95% CI 12.9-24.8). In total, 138 (63%) pts received palliative
CTX only, while 81 (37%) pts were resected in curative intent. Median
disease-free survival (DFS) in the latter pts was 12.3 months (95% CI 9.7-
23.1), with a median OS of 39.2 months (95% CI 36.0-48.4). e median
OS from start of palliative CTX (OSpall) was 10 months (95% 8.6-12.4).
Based on the evaluated SIR markers, we created a combined Systemic
Inammatory Score (SIS), which signicantly correlated with ORR, PFS
and OSpall. Pts with high SIS (≥2) had a signicantly reduced OSpall com-
pared to pts with SIS 0 (HR for SIS 2: 6.82, 95% CI 2.32-20.07, p<0,001 and
HR for SIS 3: 15.9, 95% CI 4.99-50.66; p<0,001). In multivariate analysis
for OSpall and PFS including known prognostic markers, only the Eastern
Oncology Cooperative Group performance score (ECOG) and the SIS
were independent prognostic factors (ECOG HR 1.91, 95% CI 1.15-3.15,
p<0.012; SIS HR 3.16 95% CI 1.79-5.57, p<0.001).
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts82
Conclusions: We identied a new, easily applicable SIS based on routinely
assessed serum markers as independent prognostic risk score, which has
potential to support therapeutic decision-making in pts with advanced
iCCA treated with systemic CTX.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organiser KUKM GmbH and KUKM
can disclose them if needed.
355
Comparison of esophagectomy and gastrectomy in patients
with adenocarcinoma of the esophagogastric junction (AEG)
type II – a retrospective cohort study on overall, recurrence
free survival and recurrence rates
Roman Stürzl1; Michael Gerken2,3; Monika Klinkhammer-Schalke2,3;
Armin Pauer2,3; Pompiliu Piso4
1University of Regensburg, Faculty of Medicine, Regensburg, Deutschland
2Tumor Center , Institute for Quality Management and Health Services Research,
University of Regensburg, Regensburg, Deutschland
3Bavarian Cancer Registry, Regional Centre Regensburg, Bavarian Health and
Food Safety Authority, Regensburg, Deutschland
4Hospital Barmherzige Brüder Regensburg, Clinic for General and Visceral
Surgery, Regensburg, Deutschland
Background: e incidence of adenocarcinoma of the esophagogastric
junction (AEG) has signicantly increased. However, the best surgical
therapy for cardiac cancer AEG type II is still subject of current research.
e goal of this retrospective cohort study is to compare survival and
recurrence rates in patients, who underwent either thoracoabdominal
esophagectomy (TAE) or transhiatal extended gastrectomy (TEG).
Methods: e study is based on a cohort of 323 patients diagnosed with
AEG type II between 2002 and 2020, recorded by the population-based
clinical cancer registry of Tumor Center Regensburg. Of the included
patients 63 underwent TAE and 209 TEG. In order to compare overall sur-
vival, recurrence rates, and recurrence free survival, we applied Kaplan-
Meier-method, uni- and multivariable Cox-regression and in addition 1:3
propensity score matching (PSM, n=185), to avoid confounding bias.
Result: Our analysis showed no statistically signicant dierence con-
cerning overall survival, with a trend towards higher survival rates aer
TAE (p=0,333). In contrast a trend towards higher cumulative recurrence
rates, especially for distant metastases, was found aer TAE (p=0,201),
which was signicant aer PSM (p=0,049). is trend was not observed
for the time aer 2016 (p=0,993), in which over 50% of TAE were per-
formed. No dierences were found regarding recurrence-free survival
(p=0,772).
Discussion: Our ndings in a rather small cohort are concordant to
most studies showing a trend towards better survival aer TAE. Another
German study found no signicant dierence regarding recurrence free
survival as well.
Conclusion: Both approaches seem reasonable in treatment of AEG type
II. A non-signicant trend towards TAE concerning overall survival could
be demonstrated. TEG showed a slight benet concerning recurrence
rates.
Disclosure Statement: e authors declare no conict of interest.
357
Ramucirumab beyond progression plus TAS 102 in patients
with advanced or metastatic adenocarcinoma of the stomach
or the gastroesophageal junction, after treatment failure on
a ramucirumab based therapy - nal results of the phase II
RE-ExPEL study
Thorsten O. Goetze1; Alexander Stein2; Sylvie Lorenzen3; Eray Gökkurt2;
Timursah Habibzade4; Peter Herhaus3; Disorn Sookthai1; Claudia Pauligk1;
Kristina Ihrig1; Salah-Eddin Al-Batran1
1Institut für Klinische Krebsforschung IKF GmbH am Krankenhaus Nordwest,
Frankfurt am Main
2Hämatologisch-Onkologische Praxis Eppendorf (HOPE) , Facharztzentrum
Eppendorf, Hamburg
3München Klinikum rechts der Isar der TU München , II. /III. Medizinische Klinik
und Poliklinik, München
4Krankenhaus Nordwest, University Cancer Center Frankfurt
Background: Based on results of prior trials, it seems promising to
combine Ramucirumab (Ram) beyond progression (PD) with TAS-102
(triuridine/tipiracil). e purpose of RE-ExPEL is to investigate the tol-
erability, safety and benet of Ram beyond PD in combination with TAS-
102 in advanced esophagogastric adenocarcinoma (EGA).
Methods: is is a multicenter, non-randomized, open-label investigator
initiated pilot trial. 20 Ram-pretreated patients (pts) with advanced EGA
were enrolled to a maximum of 4 cycles of ram 8mg/kg every 2 weeks
(days 1, 15 qd28) plus TAS-102 35 mg/m2/p.o. bid (d1-5 and d8-12 qd28).
Primary endpoint (EP) is tolerability and toxicity, dening a positive trial
if SAE rate according (acc.) to CTCAE 5.0 will increase less than 30% (up
to 55%) compared with results from TAGS (SAE-rate 43%) . Secondary
EPs are further safety and ecacy data. Safety evaluation was conducted
when the last patient received two cycles or prematurely discontinued
(EOT for any reason).
Result: 20 pts were enrolled between Oct 2020 and Aug 2021, 20% gas-
tric and 80% GEJ- cancers, 55% of pts with ECOG 0. Results of the nal
analysis showed that only 25% of pts had at least one SAE and the total no.
of SAEs was only 8, all without relation to systemic therapy, no SUSAR
reported. No SAE showed fatal outcome. RE-ExPEL was able to show a
median OS of 8.44 mo and a DCR of 60%.
Discussion: e safety data showed a favorable safety prole with less tox-
icity for Ram+TAS-102, maybe due to the long disease stabilization and
therefore less tumor associated symptoms. Regarding the primary safety
EP, the trial was positive with even a decrease in SAE rate compared with
TAGS.
Conclusion: Ram + TAS-102 in pts with advanced EGA beyond PD
showed a favorable safety prole. Furthermore, RE-ExPEL was able to
show very promising ecacy data for the combination Ram+TAS-102
with median OS of 8.44 mo. Ram+TAS-102 seems to be more eective
than TAS-102 alone acc. to TAGS-trial respecting the limitation of the one
arm study design with only 20pts. e combination needs further evalua-
tion in a randomized phase III trial.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 83
399
Characterization of Pontin, Reptin and CD82 in Esophageal
Adencocarcinoma
Alexandra Ludwig; Beate Limberger; Orestis Lyros; Ines Gockel;
René Thieme
Universitätsklinikum Leipzig, Klinik und Poliklinik für Viszeral-, Transplantations-,
Thorax- und Gefäßchirurgie, Leipzig, Deutschland
Background: e incidence of esophageal adencocarcinoma (EAC)
has increased in the Western world. Regardless to improved periopera-
tive chemotherapies and surgical approaches, the prognosis for EAC in
advanced stages is poor. Pontin (RUVBL1) and Reptin (RUVBL2) are
associated with the chromatin remodeling complexes, transcription reg-
ulation, DNA damage response and the Wnt/ß-Catenin pathway. eir
overexpression has been reported in several cancer entities. CD82 (KAI1)
is a tumor suppressor gene, and its lack is related to metastasis formation
and cancer progression. Transcriptional activity of CD82 might be regu-
lated by Pontin and Reptin.
Methods: An in vitro cell model for the Barrett’s esophagus (squamous
epithelium (EPC1 and EPC2), metaplasia (CP-A), dysplasia (CP-B) and
esophageal adenocarcinoma (OE33, OE19, SK-GT-4, FLO-1)) has been
used. Pontin mRNA expression was analyzed in 5-FU treated OE33 and
OE19 cells for 24h by q-RT-PCR and western blot analyses. Antisense
LNA Oligonucleotides (GapmeRs, Qiagen) were used to achieve a tran-
sient knockdown of CD82 in OE33 and OE19.
Result: Pontin and Reptin were expressed in all investigated cell lines
and both showed a signicant overexpression in CP-B, OE19 and FLO-1
cells on mRNA level. Expression of CD82 was shown to be present in all
cell lines, except in the metaplastic cell line CP-A. A signicantly lower
expression was observed in CP-A, OE33 and SK-GT-4 cells. e Pontin
mRNA expression was increased aer 5-FU exposure in OE33 and FLO-
1, whereas SK-GT-4 showed a decrease. CD82 was downregulated by
36-62% in OE33 and by 38-52% in OE19.
Discussion: Increased expression levels of Pontin and Reptin and their
contribution to the Wnt/ß-Catenin pathway activation could be a novel
biomarker in the progression of EAC. Low expression levels of CD82
might inuence the metastatic ability of EAC cells.
Conclusion: Further molecular characterizations are needed to elucidate
their impact on cell proliferation, cellular motility, Wnt-pathway activa-
tion, and their role in the carcinogenesis of EAC.
Disclosure Statement: e authors declare no conict of interest.
425
Atezolizumab plus Bevacizumab in second or further line
therapy in patients with advanced stage hepatocellular
carcinoma (HCC): data on ecacy and safety from a
multicenter real-life cohort
Friedrich Sinner1; Matthias Pinter2,3; Bernhard Scheiner2,3;
Thomas J. Ettrich4; Niklas Sturm4; Maria Angeles Gonzalez-Carmona5;
Oliver Waidmann6,7; Fabian Finkelmeier6,7,8; Vera Himmelsbach6;
Enrico De Toni9; Najib Ben Khaled9; Raphael Mohr10; Thorben Fruendt11;
Fabian Kütting12; Florian van Boemmel13; Sabine Lieb13; Sebastian Krug14;
Dominik Bettinger15; Michael Schultheiss15; Leonie Jochheim16; Jan Best1,17;
Christian Müller1; Marino Venerito1
1Department of Gastroenterology, Hepatology and Infectious Diseases,
Otto-von-Guericke University Hospital Magdeburg, Magdeburg, Deutschland
2Division of Gastroenterology and Hepatology, Medical University of Vienna,
Department of Internal Medicine III, Vienna, Österreich
3Liver Cancer (HCC) Study Group Vienna, Medical University of Vienna, Vienna,
Österreich
4Department of Internal Medicine I, Ulm University Hospital, Ulm, Deutschland
5Department of Internal Medicine I, University Hospital of Bonn, Bonn,
Deutschland
6Department of Gastroenterology, Hepatology and Endocrinology, University
Hospital Frankfurt, Frankfurt (Main), Deutschland
7University Cancer Center Frankfurt, University Hospital Frankfurt, Frankfurt
(Main), Deutschland
8Frankfurt Cancer Institute, Goethe University Frankfurt, Frankfurt (Main),
Deutschland
9Department of Medicine II, University Hospital, LMU Munich, Munich,
Deutschland
10Department of Hepatology & Gastroenterology, Charité University Medicine
Berlin, Campus Virchow Klinikum and Campus Charité Mitte, Berlin, Deutschland
11Department of Internal Medicine, Gastroenterology & Hepatology, University
Medical Center Hamburg-Eppendorf, Hamburg, Deutschland
12Clinic for Gastroenterology and Hepatology, Faculty of Medicine and University
Hospital Cologne, University of Cologne, Cologne, Deutschland
13Division of Hepatology, Department of Medicine II, Leipzig University Medical
Center, Leipzig, Deutschland
14Department of Internal Medicine I, Martin-Luther-University Halle-Wittenberg,
Halle, Deutschland
15Department of Medicine II, Medical Center University of Freiburg, University of
Freiburg, Freiburg, Deutschland
16Department of Gastroenterology and Hepatology, University Hospital Essen,
Essen, Deutschland
17Department of Internal Medicine, University Hospital
Knappschaftskrankenhaus Bochum, Ruhr University Bochum, Bochum,
Deutschland
Background: Atezolizumab plus Bevacizumab (Atezo/Bev) is the stan-
dard of care in rst line systemic therapy for advanced stage hepatocellular
carcinoma (HCC). Data on ecacy and safety of Atezo/Bev in patients
who did not have access to this option as rst line therapy are lacking.
Methods: Patients with HCC who received Atezo/Bev in second or fur-
ther lines between December 2018 and March 2022 were retrospectively
identied across 13 centers in Germany and Austria. Patient characteris-
tics, tumor response rates, progression free survival (PFS), overall survival
(OS) and adverse events (AE) were analyzed.
Result: Overall, 50 patients were identied, 41 (82%) were male. e
median age at the start of Atezo/Bev was 65 years, 41 (82%) patients had
liver cirrhosis, 30 (73%) Child A, 9 (22%) B and 2 (5%) C. e most com-
mon etiologies for the underlying liver disease were nonalcoholic fatty
liver disease (NAFLD) in 14 (28%), alcohol abuse in 13 (26%), hepatitis
C virus (HCV) infection in 11 (22%) and hepatitis B virus (HBV) infec-
tion in 6 (12%) cases, respectively. Overall, 34 patients (68%) received
Atezo/Bev in second line and 16 (32%) in further lines. Best radiologi-
cal tumor responses were complete remission in 1 (2%), partial remis-
sion in 15 (30%), stable disease in 18 (36%) and progressive disease in
9 (18%) patients resulting in a disease control rate of 68% and an objec-
tive response rate of 32%. Median OS was 16.0 months (95% condence
interval 5.6-26.4 months). Median PFS on Atezo/Bev was 7.1 months
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts84
(95% condence interval 4.4-9.8 months). Adverse events (AE) grade 3-4
were observed in 7 (14%) and led to death of 3 patients (6%). ere were
5(10%) bleeding events of grade ≥ 3, one of them (2%) with fatal outcome
was reported.
Discussion: e identication of risk factors for severe complications may
further improve the outcome in patients with advanced HCC receiving
Atezo/Bev.
Conclusion: Atezo/Bev is eective in patients with advanced stage HCC
who did not have access to this option as rst line therapy. e safety pro-
le was consistent with previous reports.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organiser KUKM GmbH and KUKM
can disclose them if needed.
428
Tertiary lymphoid structures in PDAC resemble lymphoid
follicles in secondary lymphoid organs by organization,
function and gene expression
Jonas Lehmann1; Martin Thelen1; Simon Schran1; Ella Preugszat1;
Kerstin Wennhold1; Maria Garcia-Marquez1; Philipp Lohneis2; Heike Löser2;
Felix Popp3; Michael von Bergwelt-Baildon1,4,5; Christiane J. Bruns3;
Alexander Quaas2; Hans. A. Schlößer1,3
1University of Cologne, Faculty of Medicine and University Hospital Cologne,
Center for Molecular Medicine Cologne, Köln, Deutschland
2University of Cologne, Faculty of Medicine and University Hospital Cologne,
Institute of Pathology, Köln, Deutschland
3University of Cologne, Faculty of Medicine and University Hospital Cologne,
Department of General, Visceral, Cancer and Transplantation Surgery, Köln,
Deutschland
4LMU Munich, LMU clinic, Department of Internal Medicine III, München,
Deutschland
5Deutsches Krebsforschungszentrum, DKTKDas Deutsche Konsortium für
translationale Krebsforschung, Heidelberg, Deutschland
Background: Tertiary lymphoid structures (TLS) are gaining attention
in the recent years as secondary lymphoid organs (SLO) like structures,
which are involved in induction and enhancement of anti-tumor immune
responses. ese TLS are induced or enhanced in the tumor microenvi-
ronment and are assumed to represent hotspots for T cell priming, B cell
activation and dierentiation, which cause cellular and humoral anti-tu-
mor immune responses
Methods: We performed immunohistochemistry staining of 120 primary
pancreatic ductal adenocarcinoma (PDAC) patients for CD20, CD3, CD8,
FOXP3 and FDCM1 to analyze spatial distribution of tumor-inltrating
lymphocytes. Comparison of structural components of lymphoid follicles
between TLS and SLOs was done by 5-color immunouorescence stain-
ing. Tissue extraction by laser microdissection and Nanostring-base RNA
expression analysis was conducted to compare gene expression in TLS,
PDAC, SLOs and normal pancreatic tissue.
Result: TLS were found in 85 % of all patients, but frequency of TLS dif-
fered between patients. While TLS were mainly localized in a 2000 µm
invasive tumor margin 50 % of all patients showed at least a few intra-
tumoral TLS. Patients with high density of TLS inside and surrounding
the tumor, as well as high T cell inltration showed higher overall sur-
vival. Five-color Immunouorescence revealed similarities in the archi-
tecture of TLS with secondary lymphoid organs. Nanostring analysis of 12
patients conrmed also functional similarities of TLS and SLOs by largely
overlapping expression patterns.
Discussion: As described before our results conrm benecial impact of
TLS abundance in the tumor microenvironment in PDAC. Our study is
the rst comparing the immune functional expression patterns between
SLOs and TLS in PDAC.
Conclusion: Our results indicate the close similarities of TLS and SLOs
in organization, function and gene expression patterns for better under-
standing of the tumor microenvironment in PDAC and improvement of
future therapies.
Disclosure Statement: e authors declare no conict of interest.
443
Ecacy and safety of atezolizumab and bevacizumab in the
real-world treatment of advanced hepatocellular carcinoma:
experience from four tertiary centers
Vera Himmelsbach1; Matthias Pinter2,3; Bernhard Scheiner2,3;
Marino Venerito4; Friedrich Sinner4; Carolin Czauderna5,6;
Jens U. Marquardt5,6; Jörg Trojan1; Oliver Waidmann1,7;
Fabian Finkelmeier1,7,8
1University Hospital Frankfurt, Frankfurt, Department of Gastroenterology,
Hepatology and Endocrinology, Frankfurt am Main, Deutschland
2Medical University of Vienna, Vienna, Austria , Division of Gastroenterology and
Hepatology, Department of Internal Medicine III, Wien, Österreich
3Medizinische Universität Wien, Liver Cancer (HCC) Study Group Vienna , Wien,
Österreich
4Otto-Von Guericke University Hospital, Magdeburg, Germany, Department
of Gastroenterology, Hepatology and Infectious Diseases, Magdeburg,
Deutschland
5University Medical Center, Campus Lübeck, Department of Medicine I, Lübeck,
Deutschland
6Johannes Gutenberg-Universität Mainz, Department of Internal Medicine I,
Mainz, Deutschland
7University Hospital Frankfurt, University cancer center Frankfurt, Frankfurt am
Main, Deutschland
8Goethe University Frankfurt am Main, Frankfurt Cancer Institute , Frankfurt am
Main, Deutschland
Purpose: e present multicenter cohort study aimed at assessing the e-
cacy and safety of atezolizumab and bevacizumab (A+B), the new rst line
therapy for advanced HCC, in a real-life setting.
Methods: We included prospectively collected patients with advanced
HCC receiving rst-line treatment with A+B at four cancer centers
in Germany and Austria between December 2018 and August 2021.
Demographics, overall survival (OS) and adverse events were evaluated
until September 15th, 2021.
Results: In total we included 66 patients. e median age was 66 years
and 54 (82%) were male. Predominantly underlying liver disease was
alcohol-related liver cirrhosis in 24 patients (36%) and NASH/NAFLD in
18 patients (27%). Most patients had compensated cirrhosis (n=34; 52%),
while Child-Pugh class B was observed in 23 patients (35%) and class
C cirrhosis in 5 patients (8%). 27 patients (41%) died during follow-up.
During a median follow-up period of 211 days from A+B treatment initi-
ation, median OS was not reached. e estimated survival rate was 66% at
6 months and 56% at 12 months. Patients with compensated cirrhosis had
an estimated survival rate of 85% at 6 and 78% at 12 months. In 22 patients
(33%), the administration of bevacizumab was paused during the course
of therapy, mostly due to perceived elevated bleeding risk. 14 patients
(21%) developed gastrointestinal bleeding events during A+B treatment.
One patient died in association with gastrointestinal bleeding.
Discussion: e high bleeding incidence highlights the importance of
endoscopic variceal screening before and during A+B therapy.
Conclusions: Based on the good ecacy and safety results derived from
the phase 3 study (IMBRAVE150), A+B is now considered the new stan-
dard of care for advanced, unresectable HCC. Patients in a real-world
clinical practice had more advanced liver disease and therefore showed
lower survival at 6 and 12 months so far.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 85
490
Characterization of Premalignant and Malignant Pancreatic
Cancer Cells in a Physiological and Inamed Hepatic
Microenvironment
Claudia Seemann; Svenja Quaester; Silje Beckinger; Tina Daunke;
Lisa-Marie Philipp; Isaac Musong Mboni Johnston; Susanne Sebens
Institut für Experimentelle Tumorforschung, Christian-Albrechts-Universität zu
Kiel, UKSH, Campus Kiel, Haus U30, Kiel, Deutschland
Background: Most pancreatic ductal adenocarcinomas (PDAC) are diag-
nosed at an advanced stage oen already with distant metastases. e liver
is the main site of metastasis and patients who could undergo surgical
resection of primary PDAC oen develop liver metastases aer or even
during adjuvant therapy. us, this study investigated whether the hepatic
microenvironment (HME) impacts metastasis-associated processes in
premalignant and malignant pancreatic ductal epithelial cells (PDEC).
Methods: To analyze the impact of the HME on PDEC, premalignant
H6c7-Kras (Kras) and malignant PancTu1 PDEC were indirectly cocul-
tured with hepatic stellate cells (HSC), representing a physiological HME
or hepatic myobroblasts (HMF), simulating an inamed HME. Aer
5 days, proliferation was measured via vital cell count and Ki-67 uo-
rescence activated cell scanning (FACS). PDEC were also characterized
regarding an Epithelial-Mesenchymal-Transition (EMT) phenotype and
cancer stem cell (CSC) properties using colony formation assay (CFA) and
single and combined FACS staining.
Result: We demonstrated an increased cell growth of PDEC aer cocul-
ture with HMF compared to HSC. Aer HSC coculture, Kras cells formed
a signicantly higher number of colonies compared to HMF coculture,
which was observed by trend also in PancTu1 cells. Ki-67 FACS stain-
ing revealed two PDEC populations which were similar in all cocoltures:
Ki-67 high (90%) and low (10%). Ki-67 high proliferating PDEC were
characterized by a CSC and mesenchymal phenotype, an eect which was
more pronounced in PancTu1 than in Kras cells.
Discussion: ese data indicate that HME in dependence on the inam-
matory status is an important determinant for cell growth along with
EMT and CSC properties in premalignant and malignant PDEC.
Conclusion: Overall, these ndings support the view that a physiological
HME is able to control PDEC growth and contribute to maintenance of
CSC properties while an inamed HME strongly promotes proliferative
activity of PDEC.
Disclosure Statement: e authors declare no conict of interest.
492
Implementation and benet of the S3 guideline in resected
pancreatic cancer: results of a population-based multicenter
registry study in East Bavaria
Julia Gumpp1; Alina Kupper1,2; Michael Gerken2,3; Armin Pauer2,3;
Monika Klinkhammer-Schalke2,3; Bettina M. Rau1
1Abteilung für Allgemein-, Viszeral- und Thoraxchirurgie, Klinikum Neumarkt,
Neumarkt in der Oberpfalz, Deutschland
2Tumorzentrum Regensburg - Institut für Qualitätssicherung und
Versorgungsforschung, Universität Regensburg, Regensburg, Deutschland
3Regionalzentrum Regensburg, Bayerisches Krebsregister, Bayerisches
Landesamt für Gesundheit und Lebensmittelsicherheit, Regensburg,
Deutschland
Background: In 2007, the rst German S3-guideline for exocrine pan-
creatic cancer was published. In a retrospective cohort study we investi-
gated the degree of implementation and possible eects of the guideline
recommendations in patients with resectable pancreatic cancer in clinical
routine practice.
Methods: Based on the data from the clinical cancer registry at the
Regensburg Tumor Center, two patient groups with resectable pancreatic
ductal adeocarcinoma in stages UICC I-III were analyzed. Group 1: treat-
ment period 2000-2007 (n = 88) and group 2: treatment period 2008-2017
(n = 307) were compared with regard to patient and tumor characteristics,
surgical technique, adjuvant/additive chemotherapy and overall survival.
Result: In group 2, patients’ age, (p < 0.001), comorbidities (p = 0.002),
and lower tumor stages (p = 0.022) were signicantly higher/more fre-
quent than in group 1. e percentage of patients undergoing preoperative
tumor board discussion rose from 9.3% to 43.4% (p < 0.001). Postoperative
tumorboard discussions rose from 32.6% to 87.7% (p < 0.001). e mean
number of dissected and examined lymph nodes increased from 14.5
to 19.2 (p < 0.001), whereas the percentage of R1-resections remaind
unchanged. In group 2, 67.1% of the patients received adjuvant/addi-
tive chemotherapy compared to only 38.6% in group 1 (p < 0.001). e
median overall survival was 26.9 in group 2 and 19.5 months in group 1
(HR 0.805; 95 % CI 0.622-1.041; p = 0.098). Aer adjusting for risk fac-
tors, group 2 showed a signicantly better survival compared to group 1
with an HR of 0.736 (95% CI 0.559-0.971; p = 0.030).
Discussion: e limitations of a retrospective cohort-study were ade-
quately addressed by risk-adjustment with multivariable regression
analyses.
Conclusion: Our results show a good implementation and acceptance of
the S3-guideline recommendations in resected exocrine pancreatic can-
cer in clinical practice. A signicant rise of interdiciplinary tumor board
discussion and adjuvant/additive chemotherapy aer resection seems to
contribute to an increase of overall survival.
Disclosure Statement: e authors declare no conict of interest.
529
Patient blood Management in thoracoabdominal
esophagectomy
Thorsten Perl1; Ina Maria Eberhardt2; Silvia Flachs-Nóbrega1;
Michael B Ghadimi1
1Universitätsmedizin Göttingen, Klinik für Allgemein-, Viszeral- und
Kinderchirurgie, Göttingen, Deutschland
2Universitätsmedizin Göttingen, Klinik für Anästhesiologie, Göttingen,
Deutschland
Background: Patient blood management (PBM), is a systemic quality
improvement measure to reduce anemia and need of transfusion. For
patients with a preoperative anemia and planned surgery and a transfu-
sion probability of > 10% preoperative steps for hemoglobin (Hb) opti-
mization are recommended. We describe the incidence of preoperative
anemia and transfusion requirement in patients scheduled for thorac-
ic-abdominal esophagectomy in esophageal cancer.
Methods: In a retrospective 1-year chart-analysis, we investigated patients
scheduled for thoracic-abdominal esophagectomy. Preoperative hemo-
globin (Hb), intra- and postoperative transfusion and length of stay
were assessed. Descriptive analysis with values in number (%) and mean
(+/-SD).
Result: 47 patients with thoracic-abdominal esophagectomy have been
included (all year 2019), aged 65.4 (+/- 8) years. 2 patients (4.3%) with
intraoperative (intraOP) transfusion, 7 patients (14.9%) postoperative
(postop) transfusion. All patients were discharged from ICU aer 88.9
(+/- 82.1) h. 13 patients (27.5%) with a preOP Hb of > 13 g/dl received no
transfusion intraOP, 2 (15.4%) a transfusion on ICU. 20 patients (42.6%)
were slightly anemic (preOP Hb ≤ 13 g/dl and > 11 g/dl) and required no
transfusion intraOP, 2 (10%) transfusion on ICU. 14 patients (29.8%) were
distinct anemic (preoperative Hb ≤ 11 g/dl), 1 required transfusion during
surgery, 3 (21.4%) postOP transfusion.
Discussion: We observed with 72.4% a high incidence of preOP anemia
in patients scheduled for thoracoabdominal esophagectomy. e intraOP
transfusion requirement was with 4.3% low, not indicating further PBM
procedures. e high incidence of anemia is due to preoperative onco-
logic treatment, malnutrition, and cancer-associated blood loss plausible.
For further elucidation and preoperative treatment, further diagnostics
are necessary.
Conclusion: e high incidence of preoperative anemia is not direct con-
catenated with transfusion requirement in investigated patients.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts86
624
Cancer Cachexia in pancreatic adenocarcinoma, prognostic
and predictive parameters in a predened longitudinal
observation
Johanna Meyer-Knees1; Janina Falkenthal2; Christopher Neumann1;
Annika Kurreck1; Annabel Alig1; Thomas Malinka3; Johann Pratschke3;
Hanno Riess1; Sebastian Stintzing1; Uwe Pelzer1
1Department of Internal Medicine, Division of Hematology, Oncology and
Tumorimmunology, Charité Campus Mitte, Charité - Universitätsmedizin Berlin,
Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin,
and Berlin Institute of Health, Berlin, Deutschland
2konZ·E·B·T care GmbH Zentrum für Ernährung, Beatmung und Therapie, Berlin,
3Department of Surgery, Charité Campus Mitte & Campus Virchow Klinikum,
Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität
Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin,
Deutschland
Purpose: Cachexia is frequently observed in pancreatic ductal adeno-
carcinoma (PDAC) and is responsible for impaired prognosis. Aim of
this project was to nd predictive and prognostic parameters to identify
patients (pts) at high risk for severe forms of cachexia induced impaired
survival. We focused on systemic inammatory biomarkers.
Methods: 182 pts with PDAC (n=120) and other GI malignancies (n=62,
control) were included in a prospective database and were retrospectively
evaluated according to predetermined parameters (IL-6, CRP, hemoglo-
bin, albumin, CA19-9, the body mass index, bioelectrical assessments).
We used Kaplan-Meier calculations, log-rank tests, Cox survival mod-
els, univariate, and multivariate regression to determine signicant
correlations.
Results: Pts with elevated inammatory marker serum levels had
impaired survival (OS). Pts with CRP levels above 5 mg/L had a median
OS of 12.95 [95% CI: 10.39 – 15.51] months, pts with CRP below ≤5mg/L
had a median OS of 21.08 [95% CI:18.07 – 24.09] months (p = <.001). Pts
with IL-6 levels above >4 pg/ml had a median OS of 15.90 [95% CI 14.48
17.33] months, pts with IL-6 levels below ≤4 pg/ml had a median OS of
21.08 [95% CI 19.00 – 23.17] months (p = .054). In the multivariate Cox
proportional hazard model both, CRP (HR 1.011, 95% CI 1.003 – 1.020,
p= .010) and IL-6 (HR 1.019, 95%CI 1.000 – 1.038, p = .046), were shown
to be independent prognostic factors for survival. e change in serum
levels of IL-6, but not of CRP, over the course of disease had a signicant
impact on survival. In the control group with other GI malignancies, none
of the inammatory serum marker had a prognostic value.
Conclusions: For pts with PDAC, inammatory markers are prognos-
tic factors for impaired survival, presumably due to the presence of the
accompanying cancer-induced cachexia that is specic to PDAC pts. IL-6
and CRP are sucient surrogate markers to detect risk pts. Our ndings
underlines the importance of further research, investigating these mark-
ers’ as target for therapeutic decisions and interventions.
Disclosure Statement: e authors declare no conict of interest.
643
Functional characterization of Cytoskeleton-Associated
Protein 4 (CKAP4) in esophageal adenocarcinoma cells
Beate Limberger1; Alexandra Ludwig1; Ines Gockel1; Orestis Lyros1;
Renè Thieme1
1Universitätsklinikum Leipzig, Klinik und Poliklinik für Viszeral-,
Transplantations-, Thorax- und Gefäßchirurgie
Background: Barretts esophagus (BE) predisposes to the development of
esophageal adenocarcinoma (EAC). While the incidence of EAC is rap-
idly increasing, its prognosis remains poor. Consequently, the discovery
of new molecular targets for an ecient characterization of EAC patients
is necessary. CKAP4 has been attributed to be increased in various cancer
entities and has a role in tumorigenesis. However, its role in EAC is widely
unknown.
Methods: In an in vitro cell culture model of BE and EAC, CKAP4
expression levels were veried with qPCR and western blot. In OE33
and OE19 cells CKAP4-expression was reduced by transfecting the cells
with CKAP4-siRNA for 48h and 72h. In siCKAP4 transfected cells FACS
(apoptosis), western blot analysis, colony forming assays and spheroid
formation were performed. Using western blot, the impact of CKAP4-
knockdown on the phosphorylation of Akt, MAP-Kinase, GSK3ß and
ß-Catenin was investigated. Furthermore, Ki67- and p21-mRNA-expres-
sion was analyzed in siCKAP4 cells.
Result: CKAP4 was present in all cell lines of the Barrett’s sequence (squa-
mous epithelium, metaplasia, dysplasia and EAC). CKAP4 expression was
lower in OE19 cells than in OE33 cells. Western blot and qPCR analysis
conrmed an ecient siRNA-related knockdown of CKAP4 in EAC cells
aer transfection for 48h and 72h. e phosphorylation of Akt and MAP-
Kinase was decreased in OE33 cells only, suggesting a role of CKAP4
in tumor-associated proliferation, which was conrmed by a decreased
number of colonies in a colony forming assay and smaller spheroids in
siCKAP4 cells.
Discussion: e role of CKAP4 is barely investigated in EAC at this time.
Based on our current results, it can be assumed, that CKAP4 is important
for EAC cell growth and proliferation.
Conclusion: CKAP4 is a Dickkopf-1 (DKK1) receptor and the DKK1-
CKAP4-axis might promote cell proliferation independently to the Wnt-
pathway. A further CKAP4 characterization is necessary, particularly
focusing on the CKAP4-DKK1-axis to provide more evidence for its con-
tribution in EAC development.
Disclosure Statement: e authors declare no conict of interest.
678
Meeting Medical Need - Development of a High-Throughput
Assay Using Pancreatic Cancer Patient Derived Organoids as a
Tool for Personalized Medicine
Sushmitha Sankarasubramanian1,2; Maya Niethard3,4; Christian Pilarsky2;
Christian Regenbrecht1,5,6; Lena Wedeken1
1CELLphenomics GmbH, Berlin, Deutschland
2Chirurgische Klinik, Universitätsklinikum Erlangen, Department of Surgery,
Erlangen, Deutschland
3Helios Klinikum Berlin-Buch, Department of Tumor Orthopedics, Berlin,
Deutschland
4Universitätsmedizin Greifswald, Klinik und Poliklinik für Orthopädie und
Orthopädische Chirurgie, Greifswald, Deutschland
5ASC Oncology GmbH, Berlin, Deutschland
6Universitätsklinikum Göttingen, Institute for Pathology, Göttingen,
Deutschland
Background: Pancreatic cancer is a highly heterogeneous, clinically
challenging, and oen therapy-resistant disease that is almost impos-
sible to target with a “one drug ts all” approach and therefore the
future treatment should move towards personalized medicine. Reverse
Clinical Engineering, a combined targeted phenotypic approach utilizing
patient-derived organoids allows the identication of eective treatment
in a personalized manner.
Methods: Patient tumor-derived organoids are used to perform func-
tional drug screening and the individual responses for each tumor are
identied. We developed and optimized assay conditions to use pancreatic
cancer patient-derived organoids to perform routine drug screening in a
potential high throughput manner.
Result: With this platform, we can analyze the individual tumor response
to standard of care chemotherapeutics but also novel therapeutic reg-
imen and establish a drug sensitivity prole for each individual tumor.
Using this approach, we were able to identify dierences in therapeutic
responses between dierent patient models.
Discussion: Our approach using patient-derived organoid models of
pancreatic cancer allows to identify eective treatment approaches in a
potentially personalized manner. Integrating genomic and transcrip-
tomic sequencing data to the responders and non-responders identied
in the assay will further pave the way to uncover the drug sensitive and
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 87
resistance mechanisms, potentially leading to the identication of predic-
tive biomarkers.
Conclusion: High-throughput drug screening using patient-derived
organoids possess a real opportunity to pave the way to real personalized
medicine in pancreatic cancer.
Disclosure Statement: e authors declare the following: CRAR and Christian
Regenbrecht is shareholder at CELLphenomics GmbH, a company oering drug
screens on organoid models, and ASC Oncology GmbH, a company involved in
patient specic therapy prediction.
685
Bioinformatics Analysis of the Expression and Prognosis for
BGN, COL1A1, SPARC, TIMP1 in Gastric Cancer
Chuang Yang1; René Thieme1
1Universitätsklinikum Leipzig, Klinik und Poliklinik für Viszeral-,
Transplantations-, Thorax- und Gefäβchirurgie
Background: e incidence of gastric cancer (GC) has increased world-
wide. e clinical early symptoms of GC are not obvious, and most
patients have advanced tumor stages at diagnosis. We used bioinformatics
screening tools, to assess gastric cancer biomarkers and their prognos-
tic values through the identication of key dierentially expressed genes
(DEGs).
Methods: Data sets from GC patients (GSE54129, GSE79973, and
GSE118916, GEO DataSets) were downloaded. e overlapped DEGs
and constructed protein-protein interaction (PPI) networks were identi-
ed. Aerwards, the module and hub gens were conducted by Cytoscape
soware and the relationship between hub genes and clinical information
in dierent databases including Oncomine, Gene Expression Proling
Interactive Analysis (GEPIA), e Human Protein Atlas (THPA), Kaplan-
Meier Plotter and TIMER were investigated.
Result: Top 10 hub genes were selected including FN1, IL6, COL1A1,
COL1A2, BGN, CXCL8(IL8), TIMP1, THBS2, SPARC, THBS1. e
expression levels of BGN, COL1A1, COL1A2, CXCL8, FN1, SPARC,
THBS2, TIMP1 were higher in gastric cancer tissues than in normal gas-
tric tissues. BGN, COL1A1, COL1A2, SPARC, THBS1, THBS2, TIMP1
were related to the tumor classication. BGN, FN1, SPARC, COL1A1,
TIMP1 were easier detected in tumor samples compared with normal tis-
sues. Survival analysis showed that the high expression of BGN, COL1A1,
COL1A2, FN1, SPARC, THBS2, TIMP1 were related to lower overall sur-
vival. BGN, COL1A1, SPARC, TIMP1 were signicantly associated with
the level of macrophage inltration.
Discussion: BGN, COL1A1, SPARC, TIMP1 had a higher expression in
gastric cancers than in healthy gastric mucosa and they were more related
to clinical parameters. ey may promote the development of GC by reg-
ulating the PI3K/Akt signaling pathway during the progression of GC.
Conclusion: Further researches should be conrmed in in vitro and in
vivo experiments to elucidate their impact on cell proliferation, cellular
motility, PI3K/Akt-pathway activation, and their role in the carcinogen-
esis of GC.
Disclosure Statement: e authors declare no conict of interest.
697
Immunomodulatory capacity of histone deacetylase
inhibition in esophageal adenocarcinoma due increased
HLA-ABC expression
Robert Nowotny1; Claudia Marti Grifol1; Orestis Lyros1; Ines Gockel1;
René Thieme1
1Univesitätsklinikum Leipzig, Klinik und Poliklinik für Viszeral-, Transplantations-,
Thorax- und Gefäßchirurgie
Background: HLA class I expression in highly important, as it is needed
for the presentation of tumor-associated neo-antigens. Histone deacetyl-
ase (HDAC) are responsible for epigenetic modications even in cancer
cells. Whether, the inhibition of HDACs has an Immunomodulatory
eect in cancer cells is widely unknown, especially, in esophageal adeno-
carcinoma cells (EAC).
Methods: e EAC cells OE33 and OE19 and PBMCs were treated by
six HDACi (vorinostat, DKK137, entinostat, TMP269, PCI34051 and
tubostatin A) with 300nM and 600nM for 48h. e IC50 and HLA-ABC
expression by FACS analyses were determined aer HDACi treatment.
Results: DKK137, an experimental HDACi had a sub-micromolar IC50
in OE33 (0.44µM) and OE19 (0.60µM) cells. Whereas vorinostat and
entinostat revealed IC50 values between 1-4.5µM. TMP269, PCI34051
and tubostatin A showed IC50 values > 20µM. Obviously, the HLA-ABC
expression is diverse in EAC cancer cells, as OE33 showed a 7fold higher
HLA-ABC expression than OE19 cells. Both, OE33 and OE19 cells showed
increased HLA-ABC expression when they were treated by DKK137 and
entinostat. PBMCs did not show an increase in HLA-ABC expression by
the used HDACi.
Discussion: We were able to investigate six HDACi for their anti-prolif-
erative capacity in EAC cells and their impact to the HLA-ABC surface
expression.
Conclusion: e impact of an HDACi treatment to the tumor immunol-
ogy due to a HLA-mediated increased neo-antigen presentation might be
a novel treatment concept for HDACi in EAC patients.
Disclosure Statement: e authors declare no conict of interest.
714
HEPANOVA: Final ecacy and safety results from a phase
2 study of Tumor Treating Fields (TTFields, 150 kHz)
concomitant with sorafenib in advanced hepatocellular
carcinoma (HCC)
Eleni Gkika1; Yann Touchefeu2; Teresa Macarulla Mercade3;
Antonio Cubillo Gracián4; Robert Thimme1; Thomas Brunner5;
Monika Pazgan-Simon6; Thomas Seuerlein7; Anca-L. Grosu1
1Medical Centre, University of Freiburg, Freiburg, Germany
2Hépato gastro entérologie et oncologie digestive, IMAD CHU Nantes, France
3Vall dHebrón University Hospital and Vall dHebrón Institute of Oncology,
Barcelona, Spai
4Centro Integral Oncológico Clara Campal HM CIOCC, Hospital Universitario HM
Sanchinarro, Madrid, Spain
5Medical Centre, University of Magdeburg, Magdeburg, Germany
6Department of Infectious Diseases and Hepatology, Wroclaw Medical
University, Wroclaw Medical University, Wrocław, Poland
7Department of Internal Medicine I, University Hospital Ulm, Ulm, Germany
University Hospital Ulm, Ulm, Germany
Background: Tumor Treating Fields (TTFields) are an anti-mitotic,
regional treatment modality, utilizing low intensity alternating electric
elds delivered non-invasively to the tumor using a portable medical
device. TTFields are approved by the FDA for the treatment of glioblas-
toma and malignant pleural mesothelioma. In vitro and invivoTTFields
at 150 kHz reduced the proliferative potential of hepatocelluar carcinoma
(HCC) cell lines. Most HCC patients are not amenable to curative ther-
apies and are treated with systemic treatments following failure of local
treatment options. e HEPANOVA EF-30 Phase II trial (NCT03606590)
was a prospective study investigating the ecacy and safety of TTFields
as a treatment option for advanced HCC concomitant with sorafenib. We
present the naly ecacy and saey data of the HEPANOVA trial.
Methods: Patients (N=25) with unresectable HCC not amenable to local
treatment were enrolled in this study. Patients had ECOG score 0-2;
Barcelona clinic liver cancer (BCLC) stage 0-C and measurable disease
per RECIST. Standard sorafenib treatment was administered 400 mg (2 x
200 mg tablets). TTFields (150 kHz) were delivered for 18 hours/day until
local disease progression (RECIST). Clinical follow up was performed
q4w, with CT/MRI scan q12w. Primary end point was overall response
rate (ORR); secondary: in-eld control rate, 12-month progression-free
survival rate 12 month, 1-year OS rate and incidence and severity of
adverse events.
Results: In evaluable patients (N=21), ORR was 9.5% compared to 4.5%
among historical controls (P=0.24). Disease control rate was 76%. No SAEs
were associated with TTFields. In-eld control rate at 1 year was9.5%.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts88
Discussion: Despite poor prognosis in the study population and low
exposure to study treatments versus previous studies, TTFields plus
sorafenib was safe in late-stage HCC patients.
Conclusion: Ecacy outcomes from HEPANOVA are encouraging and
warrant investigation of TTFields ecacy in HCC with a randomized,
controlled study.
Disclosure Statement: e authors declare no conict of interest.
744
Perioperative infections are a negative predictor for overall
survival in patients undergoing surgery for hepatocellular
carcinoma (HCC)
Hannah Oswald1; Sven Loosen1; Tom Luedde1; Wolfram T Knoefel2;
Christoph Roderburg1; Georg Flügen2; Markus Jördens1
1University Hospital Düsseldorf, Department of Gastroenterology, Hepatology
and Infectious Diseases, Düsseldorf, Deutschland
2University Hospital Düsseldorf, Department of General, Visceral and Pediatric
Surgery, Düsseldorf
Background: Hepatocellular carcinoma (HCC) is the most common liver
tumor and is oen dicult to treat due to the accompanying chronic liver
disease. Optimal selection of patients that benet from surgery is di-
cult. e postoperative course is oen complicated due to concomitant
diseases. Pre- and postoperative infections are oen a problem in these
patients who are immunocompromised due to their chronic liver disease.
erefore, we determined the impact of perioperative infections on the
overall survival of patients undergoing HCC surgery.
Methods: 75 patients treated at the Department of Gastroenterology,
Hepatology and Infectious Diseases or Department of General, Visceral
and Pediatric Surgery of the University Hospital Duesseldorf in the last 10
years and undergoing surgery for HCC were included. Using data avail-
able in the patients le, occurrence of infections directly before, during
or within the rst 30 days aer surgery was assessed. e postoperative
infections had to have a clear connection to the surgery performed.
Result: In total 75 patients undergoing surgery for HCC were included.
Medium age was 70 years. Median BMI was 26.0kg/m2. Median over-
all survival of our cohort was 455 days. 31 patients had a perioperative
infection, 44 had no infection. Patients with perioperative infection had
a signicantly reduced overall survival compared to patients with no
perioperative infection (360 vs. 1217 days; log rank X2(1): 8.939, p=0.003).
Discussion: We suggest that perioperative infections are a predictive
factor for overall survival in patients undergoing surgery for HCC. is
argues for a strict surveillance and treatment of possible pre- or postoper-
ative infections. Further studies with more patients need to conrm these
ndings and prospective studies are needed to try optimizing periopera-
tive settings regarding prevention of infections in this vulnerable cohort.
Conclusion: Perioperative Infections have an impact on overall survival
in patients undergoing surgery for HCC.
Disclosure Statement: e authors declare no conict of interest
784
Stereotactic body radiotherapy in the treatment of Pancreatic
Adenocarcinoma
Ahmed Gawish; Thomas Brunner
Klinik für Strahlentherapie und Radioonkologie, Magdeburg, Deutschland
Background: Pancreatic cancer is the third leading cause of cancer-re-
lated death in the United States, with a ve-year overall survival of
approximately 8%. e prognosis of advanced local pancreatic cancer is
unfavorable despite progression in therapy. Highly conformal stereotactic
body radiation (SBRT) is a developing alternative.
is research is to investigate feasibility and safety of Stereotactic Body
Radiotherapy (SBRT) in patients with locally advanced pancreatic cancer
(LAPC)
Material and Methods: For our single-institution retrospective study of
patients with pancreatic cancer treated with SBRT between 2018 and 2020,
we identied an improvement in clinical outcomes. e mean dosage was
55 Gy (with a range of 25-66 Gy) delivered in 5-12 doses. Toxicity, overall
survival, and metastasis, as well as the presence of local progression and
RECIST 1.1 response evaluation criteria in solid tumors, were all included
in the endpoint criteria.
Results: Twenty patients were treated, with a median follow-up of nine
months. Patients who received SBRT had unresectable (55%), or border-
line resectable (5 %) disease, medically inoperable (10%), or developed
local recurrence following the Whipple procedure (30%).
e median follow-up was 9 months (range 3-18 months). e actuarial 1
year local control rate was 65 %. e 2-year OS rates was 25 %. e 1-year
freedom from progression was 45 %. Median time to progression was 8
months. Two patients (10%) experienced late gastrointestinal (GI) grade
3 events.
Conclusion: For treating pancreatic cancer, SBRT might be regarded a
promising strategy that provides local control while being linked with a
slightly higher risk of late GI toxicities. It is a more convenient treatment
regimen in a shorter overall treatment time while being better tolerated
by patients.
Disclosure Statement: e authors declare no conict of interest.
786
The ecacy of the stereotactic body radiation treatment in
the management of the cholangiocarcinoma
Ahmed Gawish; Thomas Brunner
Klinik für Strahlentherapie und Radioonkologie, Magdeburg, Deutschland
Background: We provide single-institution results for people with non-
resectable locally advanced cholangiocarcinoma, both with and without
further neoadjuvant stereotactic body radiation treatment (SBRT) and
chemotherapy.
Methods and Materials: Twenty-two consecutive patients with extrahe-
patic or intrahepatic cholangiocarcinoma had SBRT and were retrospec-
tively evaluated between October 2017 and June 2021. No patient was a
candidate for a liver transplantation , however three patients underwent
a complete resection aer SBRT. SBRT was delivered in 12 fractions with
a median dose of 60 Gy. e toxicity of each participant was rated using
the CTC for Adverse Events. Using the Kaplan-Meier technique, overall
survival (OS), time to progression, and local control were calculated.
Results: e median follow-up was 15 months (range 3-29 months). e
actuarial 1 year local control rate was 85 %. e 2-year OS rates was 30 %,
with a median survival of 15.7 months. e 1- and 2-year freedom from
progression was 68% and 45 %, respectively. Median time to progression
was 13 months. 20 patients (90%) experienced some form of acute grade
1-2 toxicity, most commonly fatigue or pain. no patient experienced grade
≥3 toxicity.
Conclusions: When cholangiocarcinoma cannot be surgically removed
or in recurrence situation aer surgery, SBRT may be considered as an
alternative treatment option. It may be used as part of neoadjuvant ther-
apy or as part of denitive treatment in patients with cholangiocarcinoma.
Disclosure Statement: e authors declare no conict of interest.
789
Toxicity of the gallbladder with high-dose ablative-intent
stereotactic body radiotherapy for liver tumors
Ahmed Gawish; Thomas Brunner
Klinik für Strahlentherapie und Radioonkologie, Magdeburg, Deutschland
Purpose: e toxicity of the gallbladder from hypofractionated and ste-
reotactic body radiation treatment is not well recognized (SBRT). In a
retrospective cohort of patients with primary and metastatic liver cancers
undergoing ablative-intent, we reported on gallbladder and bile system
toxicity.
Methods and Materials: Between 2018-2021, 55 Patients underwent
SBRT of liver lesions in our department. e Patients received 56-66 Gy
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 89
in 5-12 fractions. No gallbladder dose constraints were used at treatment,
and gallbladder volumes and dose-volume histograms were created retro-
spectively. Attributable toxicity was dened as cholecystitis or perforation
without preexisting gallbladder disease. Baseline factors were evaluated
using Fisher exact test and the nonparametric K-sample test.
Results: e average duration of follow-up was 18.2 months (range, 3 -36
months).
e biliary system was irradiated with >20 Gy in 45 individuals. Twenty-
ve individuals had their gallbladders irradiated with more than 50 Gy.
Only nine individuals had bile duct stenosis; all had preexisting cholelithi-
asis and received biliary stenting before RT.
Conclusions: We found no link between gallbladder dosage and toxic-
ity and did not approach the maximum tolerable gallbladder dose in this
radiation-treated group. To preserve the gallbladder during ablative and
SBR treatments, we propose not limiting the dosage to the gross tumor
volume.
Disclosure Statement: e authors declare no conict of interest.
809
Beeinussen chronische Pankreatitisvs.
Pankreaskopfkarzinom mit pyloruserhaltender
Pankreaskopfresektion nach Traverso-Longmire
unterschiedlich das postoperative Outcome und die
mikrobielle Besiedelung - Ergebnisse eines tertiären
Zentrums
Henry Ptok1; Ronny Otto2; Ina Tammer3; Aristoteles Perrakis4;
Roland S. Croner4; Frank Meyer4
1Klinik für Allgemein- und Viszeralchirurgie, Ernst-von-Bergmann-Klinikum,
Potsdam, Deutschland
2AN-Intitut für Qualitätssicherung in der operativen Medizin, Otto-von-Guericke-
Universität zu Magdeburg mit Universitätsklinikum, Magdeburg
3Institut für Mikrobiologie, Otto-von-Guericke-Universität zu Magdeburg mit
Universitätsklinikum, Magdeburg, Deutschland
4Klinik für Allgemein-, Viszeral-, Gefäß- und Transplantationschirurgie,
Universitätsklinikum Magdeburg A.ö.R., Magdeburg, Deutschland
Operativ-therapeutisch etabliert werden Patienten(Pat.) mit chron.
Pankreatitis (CP) als auch mit Pankreaskoparzinom (CA) einer “pylo-
ruserhaltenden Pankreaskopfresektion n. Traverso-Longmire (PPPD)”
unterzogen, was eine vergl. Analyse der postop. Verläufe erlaubt.
Es wurde die ese aufgestellt, dass Pat. mit CA aufgr. der Schwere der
Tu-Erkrankung einen schlechteren Allg.- sowie Immunstatus vs. Pat. mit
CP aufweisen & sich dies im nachteiligeren frühpostop. Outcome nach
PPPD widerspiegelt.
Mit dem Ziel der Eruierung des Einusses der unterschiedl. Diagnosen
wurde das postop. Outcome aller konsekutiven Patienten, die der OP
zwischen 2002-2015 unterzogen wurden, erfasst & vergleichend aus-
gewertet. Das Outcome wurde durch die allg. & spezielle Morbidität,
die Letalität, SSI & die mikrobielle Besiedelungsrate charakterisiert.
Es wurden 308 operierte Pat. eruiert, von denen n=282 Akten auszuw-
erten waren, davon 192 Fälle mit CA (68,1%) & 90 Fälle mit CP (31,9%).
Überraschend waren die sich ähnelnden speziellen Komplikationsraten
von 45,3% (CA)vs. 45,6% (CP;p=0,97) & die 30-d-Hospital-Letalität,
welche sich mit 3,65% (CA) gegenüber 3,3 % (CP; p=0,591) nur ger-
ing unterschied. Die allg. Komplikationsrate lag bei CA mit 23,4% vs.
14,4% (CP;p=0,082) tendenziell höher. Insgesamt wurden bei CP mit
28,9% aller Pat. potenziell pathogene Keime nachgewiesen, bei CA
waren es 32,8% (p=0,509), die Rate der SSI lag bei 29,7% (CA) & 24,4%
(CP;p=0,361). In der multivariaten Analyse war CA signif. Risikofaktor
f. die Entstehung von SSI (OR: 2,025), die Grunderkrankung hatte
sonst keinen signif. Einuss auf das frühpostop. Outcome. Signif.
Risikofaktoren in der multivariaten Analyse waren außerdem das
männl. Geschlecht für SSI & die mikrobielle Besiedelung sowie intraop.
transfundierte EK‘s für die Letalität, allg. & spezielle Komplikationen.
Anhand dieser Ergebnisse wurde ein teils signif., teils tendenziell neg.
Einuss der Grunderkrankung CA, verglichen mit CP, auf das frühpostop.
Outcome gezeigt, insbes. im Hinblick auf SSI nach PPPD.
Disclosure Statement: e authors declare no conict of interest.
810
optimized PD-L 1 scoring of gastric Cancer - are biopsies able
to map the actual PD-L 1 Status of the entire Tumor?
Birgid Schömig-Markiefka1; Jana Eschbach1; Andreas Scheel1;
Aylin Pamuk2; Josef Ruescho3; Thomas Zander2; Reinhard Büttner1;
Wolfgang Schröder2; Christiane Bruns2; Heike Löser1; Hakan Alakus2;
Alexander Quaas1
1Köln, Pathologie Uniklink Köln, Köln, Deutschland
2Köln, Uniklinik Köln, Köln, Deutschland
3Kassel, Pathologie Nordhessen, Kassel, Deutschland
Purpose: PD-1/PD-L1-Immunotherapy has been approved for gastric
carcinoma. PD-L1 assessment by immunohistochemistry is the principle
biomarker. Are biopsies able to map the actual PD-L1 status of the entire
tumor?
Methods: Whole tumor slides of 56 gastric carcinoma were analyzed to
determine the distribution of PD-L1 positive cells in the entire tumor
areas. Tissue micro arrays with four cores of the tumor surface, which
represents the endoscopically accessible biopsy zone, were built from the
same tumors. e PD-L1 CPS value was determined separately for each
core. Preoperative diagnostic biopsies were available for 22 of the tumors.
PD-L1 prevalence, sensitivity and specicity were analyzed by using the
whole tumor slides as reference scores. Molecular subtyping was per-
formed and related to the PD-L1 status.
Results: 27.3% of cases were PD-L1 negative (CPS <1), 43.6% showed low
PD-L1 expression (CPS ≥1 to <5), 12.7% moderate (CPS ≥5 to <10) and
16.4% strong expression (CPS ≥10).
e biopsies showed best test characteristics if four surface biopsies were
analyzed combined, i.e. the CPS was calculated across all four biopsies.
e prevalence showed a distribution similar to the resection specimens,
sensitivity was 0.73 and specicity 1.0. Using fewer surface biopsies
decreased sensitivity and specicity and caused false-negative classica-
tions. Compared to the TMAs, the preoperative biopsies showed reduced
sensitivity (0,412).
Discussion: e obtained PD-L1 prevalence is consistent with data of
current clinical studies. Calculation of the test characteristics shows that
surface biopsies can be indicative of the true PD-L1 status based on the
resection specimen. However, an adequate number of biopsies is required.
In this study, n=4 biopsies yielded best results.
Conclusion: If at least four biopsies with a total area of about 4.5mm² are
sampled and analyzed combined, results similar to resection specimens
may be obtained.
If the PD-L1 status is determined on biopsy material, ensure a sucient
number of tumor-bearing biopsies.
Disclosure Statement: e authors declare no conict of interest.
812
sex related molecular aspects in gastrointestinal oncology - to
be aware of an emerging eld in oncology
Birgid Schömig-Markiefka1; Alexander Quaas1; Dorothea Wagner2
1Köln, Pathologie Uniklinik Köln, Köln, Deutschland
2Lausanne, lausanne Universtitätshospital (CHUV), Onkologie, Lausanne,
Schweiz
Purpose: e importance of sex and gender as modiers of health, dis-
ease and medicine is increasingly recognized. In fact, sex-related dier-
ences are a reality in multiple facets of oncology, like tumor epidemiology,
molecular biology, tumor immunology, and tumor treatment.
Methods: We used an extensive literature search in Pubmed, Medline, and
Google-Scholar as a basis as well as results of our own analysis in esopha-
geal and gastric carcinomas (n=1100 tumors) are also considered.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts90
Results: Epstein-Barr-Virus-related gastric carcinomas are predomi-
nantly found in male patients, whereas microsatellite-instable tumors in
the distal part of the stomach are found more oen in female patients.
Males develop adenocarcinomas of the esophagus (8-9:1 ratio), whereas
the underlying Barrett’s mucosa occurs in a 2-3:1 ratio.
Discussion: Why is there an increase in poorly cohesive carcinomas of the
gastric corpus predominantly in young women over the past 10 years (so
called CYF-tumor)? Why do sporadic microsatellite instable colon carci-
nomas (MSI) typically develop in older women in the right-sided colon?
How can gender-specic selection of KRAS mutation subtypes in colon
carcinoma be explained (e.g., KRAS G12C occurs disproportionately in
women)?
Conclusion: e aim is to give a good overview of the current state of
knowledge on the subject of sex-related aspects in the tumor biology of
GI-tumors (esophagus, gastric, small- and large bowel) and can help to
raise awareness of this underrepresented topic in oncology.
Disclosure Statement: e authors declare no conict of interest.
814
GP-2250, a novel anti- cancer agent, targets the energy
metabolism of pancreatic tumor cells trough inhibition of
GAPDH involve ROS, AMPK and NFkB
Britta Majchrzak-Stiller1; Marie Buchholz1; Ilka Peters1; Johanna
Strotmann1; Phillip Höhn1; Thomas Müller2; Waldemar Uhl1;
Chris Braumann1
1St. Josef Hospital Universitätsklinikum der Ruhr-Universität Bochum, Klinik für
Allgemein- u. Viszeralchirurgie, Arbeitsgemeinschaft Molekulare und Klinische
Forschung im IFL, Bochum, Deutschland
2 Geistlich Pharma AG , Wolhusen, Schweiz
Background: GP-2250, an oxathiazinan derivative, displayed selective
cytotoxicity against various tumor cells in vitro and in vivo. But the mech-
anism of action still remained unclear. Now, we were able to show that
GP-2250 acts by impairing the energy metabolism of these tumor cells
involving key enzymes like GAPDH and AMPK and transcription factors
like NFkB.
Methods: Using pancreatic cancer cell lines, we assed key enzymes of the
energy metabolism through activity assays, phosphorylation assays, and
Western blot analysis.
Result: GP-2250 is an eective cancer metabolism-based therapeutic
agent. It depletes metabolic energy, largely through inhibition of GAPDH
(glyceraldehyde-3-phosphate dehydrogenase) which is rate limiting for
aerobic glycolysis. us, GP-2250 reduces ATP in a time- and dose-de-
pendent manner and activates the energy-decit sensor AMPK as well as
several downstream targets, which curtail the growth and proliferation of
tumor cells. Additionally, the NFkB pathway was also impaired by strong
reduction of nuclear p65 binding. Cyclin D1, the driver of cell mitosis,
was correspondingly downregulated. Both, metabolic stress and oxidative
stress, through increased ROS levels, contribute to tumor cell death.
Discussion/ Conclusion: GP-2250 is expected to be of wide therapeutic
interest. Its ability to inhibit the provision of metabolic energy, especially
in pancreatic tumor cells, oers a highly promising therapeutic approach.
Disclosure Statement: e authors declare no conict of interest.
884
Stereotactic body radiotherapy for the management of
adrenal gland metastases: a bi-institutional analysis
Felix Ehret1; David Kaul1; Markus Kufeld2; Clara vom Endt1; Volker Budach1;
Christoph Fürweger2; Alfred Haidenberger2; Alexander Muacevic2
1 Charité - Universitätsmedizin Berlin
2 Europäisches Radiochirurgie Centrum
Background: Adrenal gland metastases (AGMs) are a common manifes-
tation of metastatic tumor spread, especially in non-small cell lung cancer
(NSCLC) and small cell lung cancer (SCLC). In patients with a limited
systemic tumor burden, eective treatments for AGMs are needed. Due to
varying fractionation schemes and limited reports, short-course treatment
results for stereotactic body radiotherapy (SBRT) for AGMs are lacking.
is work analyzes the outcomes of short-course SBRT for AGMs.
Methods: Patients who underwent robotic SBRT for AGMs with one to
ve fractions were eligible for analysis.
Result: Data from 55 patients with 72 AGMs from two institutions were
analyzed. Most AGMs originated from renal cell carcinoma (38%) and
NSCLC (35%). e median follow-up was 16.4 months. e median pre-
scription dose and isodose line were 24 Gy and 70%, respectively. Most
patients (85%) received SBRT with just one fraction. e median biologi-
cally eective dose assuming an α/β ratio of 10 (BED10) was 80.4 Gy. e
local control (LC) and progression-free survival aer 1 and 2 years were
92.9%, 67.8%, and 46.2%, as well as 24.3%, respectively. irteen patients
(24%) suered from grade 1 or 2 toxicities. e BED10 showed a signi-
cant impact on LC (p < 0.01). Treatments with a BED10 equal to or above
the median were associated with a better LC (p < 0.01).
Discussion: Results suggest short-course SBRT to be a preferable and
time-saving treatment option for AGMs if an adequate BED10 can be
safely applied. is is in agreement with recent analyses that suggest a
dose-response relationship, with higher BED10 ranging from 80 to over
100 Gy achieving considerable LC rates.
Conclusion: Short-course SBRT is an ecient and safe treatment modal-
ity for AGMs if a sucient BED10 is delivered. Treatment-associated side
eects are sporadic and manageable.
Disclosure Statement: e authors declare no conict of interest.
950
Extended overall survival results from the POLO study of
active maintenance olaparib in patients with metastatic
pancreatic cancer and a germline BRCA mutation
Dirk Arnold1; Pascal Hammel2; Talia Golan3; Michele Reni4;
Eric Van Cutsem5; Teresa Macarulla6; Michael J. Hall7; Joon Oh Park8;
Daniel Hochhauser9; Do-Youn Oh10; Anke Reinacher-Schick11;
Giampaolo Tortora12; Hana Algül13; Eileen M. O’reilly14; Kanu Sharan15;
Xiaoling Ou16; Karen Cui17; Gershon Y. Locker17; Hedy L. Kindler18
1Asklepios Klinik Altona, Hamburg, Deutschland
2Hôpital Paul-Brousse Ap-Hp, Villejuif, Frankreich
3Sheba Medical Center, Tel Aviv, Israel
4San Raaele Hospital, Milano, Italien
5Katholieke Universiteit Leuven, Leuven, Belgien
6Hospital Universitari Vall dHebron, Barcelona, Spanien
7Fox Chase Cancer Center, Philadelphia, USA
8Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
9UCL Cancer Institute, Vereinigtes Königreich
10Seoul National University Hospital, Cancer Research Institute, Seoul,
11St. Josef-Hospital Hörsaal - Katholisches Klinikum Bochum, Bochum,
Deutschland
12Gemelli-Klinik, Roma, Italien
13Klinikum rechts der Isar der Technischen Universität München Notaufnahme,
München, Deutschland
14Memorial Sloan-Kettering Cancer Center, New York, USA
15Merck & Co Inc, Rahway, USA
16AstraZeneca, Milton, Vereinigtes Königreich
17AstraZeneca, Gaithersburg, USA
18University of Chicago, Chicago, USA
Background: e POLO study (NCT02184195) demonstrated a signicant
progression-free survival (PFS) benet for active maintenance olaparib (O)
relative to placebo (P) for patients (pts) with metastatic pancreatic cancer
and a germline BRCA mutation (hazard ratio [HR]: 0.53, 95% condence
interval [CI]: 0.35–0.82; p = 0.004; data cut-o 1 [DCO1]). In the nal
overall survival (OS) analysis (DCO2), the HR for OS favoured olaparib
without reaching statistical signicance (HR: 0.83; 95% CI: 0.56–1.22; p =
0.3487). Here, we present an exploratory extended OS analysis, carried out
12 months aer the nal OS analysis (DCO3).
Methods: Pts (N = 154) were randomized 3:2 to O (300 mg tablets b.i.d.; n
= 92) or P (n = 62). e primary endpoint was PFS by blinded independent
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 91
central review; secondary endpoints included OS, investigator-PFS, time to
treatment discontinuation (TDT) and time to rst and second subsequent
therapies (TFST; TSST). HRs and 95% CIs were calculated using a log-rank
test.
Result: At DCO3, 26 pts (16.9%) remained in the study (O: 20.7%; P:
11.3%). e proportions of pts who remained on O or P were 38.9% vs 9.8%
at 1 year, 24.4% vs 3.3% at 2 years, 16.4% vs 3.3% at 3 years and 13.5% vs
3.3% at 4 years. e OS result at DCO3 remained similar to that at DCO2
(HR: 0.79; 95% CI: 0.55–1.15). However, the KM curves separated clearly
from 24 months aer randomization (estimated O and P survival rates:
34.4% vs 15.7% at 3 years; 23.9% vs 15.7% at 4 years; 19.2% vs 10.5% at
5 years). In total, 7.6% and 27.4% of pts in the O and P arms, respectively,
received a subsequent PARP inhibitor. Investigator-PFS, TDT, TFST and
TSST were longer for O than for P (Table). Safety results were consistent
with DCO2.
Discussion: -
Conclusion: e HR for OS continued to favour O, although the 95% CI
overlapped 1.0. e results indicate an unprecedented durable response to
O in a subset of patients.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organiser KUKM GmbH and KUKM
can disclose them if needed.
995
Second-Line and Third-Line Therapy with Nanoliposomal
Irinotecan (nal-IRI) in pancreatic cancer: A Single Center
Experience
Christian Möhring1; Freddy José Frontado Grae1; Alexandra Bartels1;
Farsaneh Sadeghlar1; Taotao Zhou1; Robert Mahn1; Milka Marinova2;
Georg Feldmann3; Peter Brossart3; Tim Glowka4; Jörg C. Kal4;
Christian P. Strassburg3; Maria Angeles Gonzalez-Carmona1
1Universitätsklinikum Bonn Medizinische Klinik und Poliklinik I, Bonn,
Deutschland
2Universitätsklinikum Bonn Abteilung für Radiologie, Bonn, Deutschland
3Universitätsklinikum Bonn Medizinische Klinik und Poliklinik III, Bonn,
Deutschland
4Universitätsklinikum Bonn Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax-
und Gefäßchirurgie, Bonn, Deutschland
Background: Prognosis of patients with pancreatic cancer (PC) is still
extremely poor. e majority of patients are only suitable for palliative
treatment. In this setting, rst-line palliative therapies with FOLFIRINOX
or gemcitabine/nab-paclitaxel have been established in the last decade. In
the second-line, 5-FU/LV in combination with nanoliposomal irinotecan
(nal-IRI) aer gemcitabine has been shown eective. In this study, we
report about the use of nal-IRI + 5-FU/LV in a daily practice setting in an
unselected cohort of patients with PC and analyzed, whether nal-IRI is an
option as third-line therapy aer prior nonliposomal irinotecan exposure.
Methods: is is a single institution retrospective analysis of patients with
irresectable PC who were treated with nal-IRI and 5-FU/LV from 2017 to
2021 as second- or third-line palliative treatment. Overall survival (OS),
progression-free survival (PFS) and toxicity were analyzed, and multivari-
ate analysis was used to identify independent prognostic factors.
Result: 29 patients receiving nal-IRI and 5-FU/LV were included in the
analysis. Median OS and PFS were 9.33 months (95% CI: 3.37, 15.30)
and 2.90 months (95% CI: 1.64, 4.16), respectively. Furthermore, patients
receiving nal-IRI + 5-FU/LV as third-line treatment (n=19) showed no
OS dierence compared to second-line patients without nonliposomal iri-
noctecan pre-exposure (n=10) (9.33 months vs. 10.27 months; HR: 1.85;
p=0.253). Baseline high CA 19-9 level (HR: 3.281) and metastatic disease
(HR: 7.123) were associated with worse OS. Adverse eects were similar
to reported trials.
Discussion: e use of nal-IRI + 5-FU/LV in unselected patients with
advanced PC showed similar OS, PFS and tolerance as randomized
prospective phase II/III trials. Interestingly, the treatment with nal-IRI
+ 5-FU/LV seemed to be benecial in the third-line therapy despite a
pre-exposure to nonliposomal irinotecan.
Conclusion: Nal-IRI + 5-FU/LV may be considered for patients with
advanced PC, even aer prior nonliposomal irinotecan therapy.
Disclosure Statement: e authors declare the following: Honorare
1001
Characterization of invasive and adhesive behavior of
pancreatic ductal adenocarcinoma cells with dierent cancer
stem cell properties
Arne Surrow1; Umut Ulas Yesilyurt1; Luisa Hattingen1; Amelie Modi1;
Lisa-Marie Philipp1; Susanne Sebens1
1Institut für Experimentelle Tumorforschung Christian-Albrechts-Universität zu
Kiel, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Haus U30/ Eingang
1, Kiel, Deutschland
Background: Pancreatic ductal adenocarcinoma (PDAC) is oen diag-
nosed at advanced stages and oen metastasizes in liver, lung and
peritoneum. During metastasis, PDAC cells undergo epithelial-mesen-
chymal-transition characterized by loss of epithelial and gain of invasive,
mesenchymal phenotype linked to the acquisition of cancer stem cell
(CSC) properties. As own data indicate the existence of mesenchymal and
epithelial CSC phenotypes in PDAC, this study aimed to investigate inva-
sive and adhesion properties of dierent CSC phenotypes.
Methods: Mesenchymal and epithelial PDAC subclones with dierent
CSC properties were characterized. Adhesion of labelled PDAC cells to
liver- and lung endothelial cells as well as mesothelial cells was analyzed
by automated microscopy. For invasion assays, PDAC cells were seeded
into ultra-low-attachment plates for spheroid formation and covered with
Matrigel. Invasive parameters were evaluated with automated microscopy.
Result: Adhesion to mesothelial and lung endothelial cells did not dier
in mesenchymal and epithelial PDAC cells with dierent CSC proper-
ties, but mesenchymal PDAC cells showed a higher adhesion rate to liver
endothelial cells than epithelial PDAC cells. Moreover, PDAC cells with a
mesenchymal CSC phenotype showed the fastest matrix invasion which
occurred in single cells or chains of single cells, while PDAC cells with an
epithelial CSC phenotype invaded much slower in clusters.
Discussion: Mesenchymal and epithelial CSC phenotypes showed dier-
ent invasion modes and adhesion to liver endothelial cells, which is in line
with distinct metastatic patterns in vivo. us, current work investigates
how knockdown of CSC markers impacts invasive behavior of PDAC cell
clones.
Conclusion: ese data indicate that PDAC cells with dierent CSC char-
acteristics dier regarding invasive behavior and putatively metastatic
potential. Future studies identifying determining factors might pave the
way for novel anti-metastatic treatment strategies.
Disclosure Statement: e authors declare no conict of interest.
1002
Carcinoma-associated broblasts and renin-angiotensin
system-based mechanotherapeutics in pancreatic cancer
Sophie He1; Thomas M. Pausch1; Naita Wirsik1; Miriam Schenk1;
Nathalia Giese1; Patrick S. Plum2; Martin Schneider1; Thilo Hackert1;
Thomas Schmidt2
1Universitätsklinikum Heidelberg, Allgemein-, Viszeral- und
Transplantationschirurgie , Heidelberg, Deutschland
2Universitätsklinikum Köln, Allgemein-, Viszeral- und Transplantationschirurgie,
Köln, Deutschland
Background: Pancreatic ductal adenocarcinoma (PDAC) has a pro-
nounced desmoplastic stroma, which plays a central role in poor ther-
apeutic response. Carcinoma-associated broblasts (CAFs) are the most
common stromal cells and of therapeutic interest. Depending on the
subpopulation they have pro- or anti-carcinogenic functions. In col-
orectal cancer, we have shown that renin-angiotensin-aldosterone sys-
tem (RAAS) inhibitors reduce CAF-induced tumor stiness, improving
antiangiogenic therapy and survival. In PDAC we have proved mutual
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts92
stimulation of tumor cells and CAFs in vitro. Further elucidation of the
role of CAFs and stromal mechanics in the context of RAAS inhibitors is
a prerequisite for therapeutic use of these established drugs. e purpose
of this study was the histological analysis of potential modulation of the
desmoplastic stroma by RAAS inhibitors and correlation with survival in
in patients with resected PDAC.
Methods: In tumor tissue of primarily resected PDAC patients (n = 47),
the eect of preoperative administration of RAAS inhibitors on tissue
stiness (Col-1, PMLC), CAF activitation (α-SMA, PDGFRα) and prolif-
eration (Ki67) was examined immunohistochemically. In parallel, clinical
correlation with survival was carried out in univariate and multivariate
analysis.
Results: Histological analysis showed a trend towards negative correlation
of the ratio of CAF activation and stroma stiness, activated stroma index
(ASI), with patient survival (ASI cut-o 0.5, p = 0.1). is correlation was
weaker in patients aer RAAS inhibitor therapy (p = 0.3).
Discussion: Validation on a larger cohort, with primary patient cells
and associated with oncological therapy will follow, in order to optimize
patient selection for possible renin-angiotensin system-based mechanoth-
erapy in PDAC.
Conclusion: RAAS inhibitors have a modulating eect on the desmoplas-
tic stroma in PDAC. is modulation does not seem to aect patient sur-
vival in primary resected PDAC.
Disclosure Statement: e authors declare no conict of interest.
1003
Real-world timelines of BRCA1/2-related molecular testing in
pancreatic cancer
Weiyan LI1; Suvina Amin1; Seongjung Joo2; Gboyega Adeboyeje2;
Patricia Dearbeloa3; Emanuel F Petricoin III3,4; Edik M Blais3;
Michael J Pishvaian3,5
1AstraZeneca, Gaithersburg, USA
2Merck, Kenilworth, USA
3Perthera, Holliston, MA , USA
4George Mason University, Fairfax, USA
5Johns Hopkins School of Medicine, Baltimore, USA
Background: Olaparib is an approved PARP inhibitor (PARPi) for germ-
line BRCA1/2-mutated metastatic PaC. e availability of BRCA1/2 test-
ing results at the time of 1st line and subsequent treatment decisions in the
advanced stage has not been established in real-world settings.
Methods: Longitudinal clinical/molecular data collected between 1/2012-
12/2020 were retrospectively analyzed in 75 PaC pts with germline or
somatic BRCA1/2 mutations (BRCA1/2m) who enrolled in Pertheras US
real-world observational registry. Tumor NGS testing results were gener-
ated by commercial labs for all patients. Germline status was assessed by
a molecular tumor board when testing results are available. BRCA1/2m
discovery timing (days since advanced presentation), molecular testing
turnaround time (days from physician order to result), and platinum uti-
lization were abstracted from physician records. Associations between
BRCA1/2m discovery timing and platinum utilization were evaluated
using Fishers exact test.
Result: At the time of advanced PaC diagnosis, BRCA1/2m status was
known in a minority of patients (29% (22 of 75). In the remaining 71%
(53 of 75) patients, the median time to report BRCA1/2m status was 76
days (IQR=56-558) following advanced diagnosis. e median tumor
NGS testing turnaround time was 35 days aer physician order (IQR=24-
54). Platinum use in any setting was documented in 85% (64 of 75) of
patients and the majority of these patients (62%, 40 of 64) initiated a plati-
num-based regimen before BRCA1/2m status was rst reported. Platinum
agents were initiated before 2nd line in 75% (48 of 64) patients, and this
was associated with BRCA1/2m identication before advanced diagnosis
(p=0.03).
Conclusion: BRCA1/2 testing results may not always be available when
1st line regimens are chosen which can impact ideal treatment sequencing
in PaC patients. ese real-world analyses underscore the importance of
upfront BRCA1/2 testing in PaC patients.
Indication of source:
1 American Society of Clinical Oncology Gastrointestinal Cancer Symposium,
Jan 20-22, 2022
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organiser KUKM GmbH and KUKM
can disclose them if needed.
1009
Clinical outcome and prognostic factors of pancreatic
adenosquamous carcinoma compared to ductal
adenocarcinoma – results from the nationwide German ADT
registry
Rüdiger Braun1; Louisa Bolm1; Kim Honselmann1; Ekaterina Petrova1;
Hryhoriy Lapshyn1; Steen Deichmann1; Monika Klinkhammer-Schalke2;
Sylke Ruth Zeissig2; Kees Kleihus van Tol3; Benjamin Heckelmann1;
Peter Bronsert4; Sergii Zemskov5; Richard Hummel1; Tobias Keck1;
Ulrich Wellner1
1Klinik für Chirurgie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck,
Lübeck, Deutschland
2Netzwerk für Versorgung, Qualität und Forschung in der Onkologie,
Arbeitsgemeinschaft Deutscher Tumorzentren (ADT), Berlin,
3Netzwerk für Versorgung, Qualität und Forschung in der Onkologie,
Arbeitsgemeinschaft Deutscher Tumorzentren (ADT), Berlin, Deutschland
4Institut für Chirurgische Pathologie, Universitätsklinikum Freiburg, Freiburg,
Deutschland
5Department of General Surgery, Bogomolets National Medical University, Kiew,
Ukraine
Background: Adenosquamous carcinoma of the pancreas (ASCP) is a
rare malignancy and it’s pathophysiology is poorly understood. Sparse
clinical data suggest that overall survival is worse in comparison to ductal
adenocarcinoma (PDAC).
Methods: Clinical outcome and prognostic factors for overall survival of
patients with ASCP in comparison to PDAC documented in the nation-
wide registry of the Association of German Tumor Centers were evaluated.
Result: 278 patients with ASCP were identied. Signicantly more
patients underwent surgical resection in the cohort of ASCP patients in
comparison to patients with PDAC (p<0.001). In the cohort of 142 sur-
gically resected patients with ASCP the majority of patients was treated
by a partial pancreatoduodenectomy (44.4%). However, compared to the
cohort of PDAC patients signicantly more patients underwent distal pan-
createctomy (p<0.001). ASCPs were signicantly more oen poorly dier-
entiated (G3) (p<0.001) and blood vessel invasion (V1) was detected more
frequently (p=0.01) in comparison with PDAC. Median overall survival
was 6.13 months (95% CI 5.20 - 7.06) for ASCP and 8.10 months (95% CI
7.93 - 8.22) for PDAC patients (p=0.094). However, when comparing only
those patients who underwent surgical resection, overall survival of ASCP
patients was signicantly shorter (11.80; 95% CI 8.20 – 15.40) compared
to PDAC patients (16.17; 95% CI 15.78 – 16.55) (p=0.007). ASCP was a
highly signicant prognostic factor for overall survival on multivariable
Cox regression analysis (HR 0.767; 95% CI 0.596 - 0.0987; p=0.039).
Discussion: ASCP showed poorer dierentiation and higher frequency of
blood vessel invasion indicative of a more aggressive tumor biology. e
surgical procedures suggest that a signicantly higher proportion of ASCP
tumors was located in the pancreatic body/tail.
Conclusion: ASCP was a negative prognostic factor for overall survival.
Overall survival of resected ASCP patients was signicantly shorter
compared to resected PDAC patients. However, surgical resection still
improves survival signicantly.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 93
1044
MATTERHORN: Ecacy and safety of neoadjuvant-adjuvant
durvalumab and FLOT chemotherapy in resectable gastric
and gastroesophageal junction cancer – a randomized,
double-blind, placebo-controlled, phase 3 study
Yelena Janjigian1; Eric Van Cutsem2; Kei Muro3; Zev Wainberg4;
Salah-Eddin Al-Batran5; Woo Jin Hyung6; Daniela Molena7; Brent Evans8;
Dario Ruscica9; Scott H. Robbins8; Alejandra Negro8; Josep Tabernero10
1Memorial Sloan Kettering, New York,
2University Hospitals Leuven and KULeuven, Leuven, Belgien
3Aichi Cancer Center Hospital, Nagoya, Japan
4David Geen School of Medicine at UCLA, Los Angeles, USA
5University Cancer Center, Frankfurt am Main, Deutschland
6Yonsei University College of Medicine, Seoul, Korea, Dem. Peoples Rep. of
7Memorial Sloan Kettering, New York, USA
8AstraZeneca, Gaithersburg, USA
9AstraZeneca, Cambridge, Vereinigtes Königreich
10Vall dHebron University Hospital, Vall dHebron Institute of Oncology,
Barcelona, Spanien
Background: Gastric/gastroesophageal junction cancers (GC/GEJC) are
the 5th most common cancers and the 3rd leading cause of cancer-re-
lated deaths globally. Standard of care for resectable GC/GEJC includes
neoadjuvant-adjuvant FLOT chemotherapy with surgery for some
regions of the world. Despite treatment advances, 5-year recurrence rate
remains high and 5-year overall survival (OS) is poor. Evidence suggests
cytotoxic chemotherapy can promote antitumor immunity, thus the
combination of immune checkpoint inhibitors, such as durvalumab (an
anti–PD-L1 antibody), with chemotherapy may result in increased e-
cacy. MATTERHORN (NCT04592913) is a Phase 3, multicenter study
evaluating the ecacy and safety of neoadjuvant-adjuvant durvalumab
or placebo with FLOT followed by adjuvant durvalumab or placebo in
patients with resectable GC/GEJC.
Methods: About 900 adult patients will be randomized 1:1 to Arm A
or B for 2 neoadjuvant and 2 adjuvant cycles (single cycle: durvalumab
or placebo every 4 weeks [Q4W] + FLOT [Q2W × 2]); followed by
durvalumab or placebo Q4W for 10 cycles. Eligible patients must have
histologically conrmed, resectable, Stage II or higher GC or GEJC
untreated with anticancer therapy, ECOG 0 or 1, and adequate organ
function. Key exclusion criteria are any prior immune-mediated therapy,
peritoneal dissemination or distant metastasis, (adeno)squamous cell car-
cinoma, or gastrointestinal stromal tumor. Primary endpoint is event-free
survival assessed by blinded independent central radiology review and/or
local pathology testing. Secondary endpoints include OS and pathological
complete response rate (pCR). Safety and tolerability will be evaluated by
adverse events, vital signs, laboratory parameters, and electrocardiogram.
Enrollment is ongoing.
Funding: AstraZeneca
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organiser KUKM GmbH and KUKM
can disclose them if needed.
1064
Dose-escalation and dose-expansion study of trastuzumab
deruxtecan (T-DXd) monotherapy and combinations in
patients (pts) with advanced/metastatic HER2+ gastric cancer
(GC)/gastroesophageal junction adenocarcinoma (GEJA):
DESTINY-Gastric03
Alexander Stein1; Florian Lordick2; Yelena Y Janjigian3; Do-Youn Oh4;
Keun-Wook Lee5; Neeltje Steeghs6; Yee Chao7; Maria DI Bartolomeo8;
Marc Díez García9; Nadia Haj Mohammad10; William Mcadoo11;
Megan Winter12; Elizabeth Croydon13; Jeeyun Lee14
1Hämatologisch-Onkologische Praxis Eppendorf, Hamburg, Deutschland
2University of Leipzig Medical Center, Leipzig
3Memorial Sloan Kettering Cancer Center, New York, USA
4Seoul National University Hospital, Seoul National University College of
Medicine, Republik Korea
5Seoul National University College of Medicine, Seoul National University
Bundang Hospital
6Netherlands Cancer Institute
7Taipei Veterans General Hospital, National Yang Ming Chiao Tung University,
Section 2
8Fondazione IRCCS Istituto Nazionale dei Tumori
9Vall dHebrón University Hospital-VHIO
10University Medical Center Utrecht
11AstraZeneca Pharmaceuticals LP, Gaithersburg
12AstraZeneca Pharmaceuticals LP, Cambridge
13AstraZeneca Pharmaceuticals
14Samsung Medical Center, Sungkyunkwan University School of Medicine,
81, Irwon-ro, Gangnam-gu, Seoul 06351 KR
Background: T-DXd is an antibody-drug conjugate of a humanized anti-
HER2 monoclonal antibody, a tetrapeptide-based cleavable linker, and
a topoisomerase I inhibitor payload. In DESTINY-Gastric01, T-DXd
showed improved ecacy vs SOC in Japanese and Korean pts (≥2 prior
therapies) with advanced HER2+ GC/GEJA. Preclinical data of T-DXd
combinations suggest encouraging antitumor activity. DESTINY-
Gastric03 is the rst study of T-DXd combinations in GC/GEJA.
Methods: DESTINY-Gastric03 (NCT04379596) is a 2-part, phase 1b/2,
multicenter, open-label, 3+3 dose-escalation (part 1) and -expansion
(part2) study. In part 1, pts with locally conrmed HER2+ GC/GEJA
(IHC 3+ or IHC 2+/ISH+) progressed on/aer ≥1 prior therapy including
a trastuzumab-containing regimen received T-DXd every 3 weeks+as-
signed combination. Primary objectives were safety and recommended
phase 2 dose (RP2D). Conrmed objective response rate (ORR) was a
secondary endpoint.
Result: In part 1, 15 pts were assigned to T-DXd+5-FU and 10 pts to
T-DXd+oral capecitabine (Cap). Starting doses were T-DXd 5.4 mg/
kg+5-FU 800 mg/m2 and T-DXd 5.4 mg/kg+Cap 1000 mg/m2 twice daily
(BID). ere were 2 dose-limiting toxicities of grade 3 stomatitis with
T-DXd 6.4 mg/kg+5-FU 800 mg/m2 exceeding maximum tolerated dose,
and was discontinued. RP2Ds were T-DXd 6.4 mg/kg+5-FU 600 mg/m2
and T-DXd 6.4 mg/kg+Cap 1000 mg/m2 BID. Preliminary conrmed and
conrmed + unconrmed ORR at the RP2D for T-DXd+Cap were 3/7
and 5/7
Discussion: -
Conclusion: DESTINY-Gastric03 preliminary part 1 results suggest tol-
erability and feasibility of the RP2Ds for T-DXd+5-FU and T-DXd+Cap.
Preliminary ORR with the T-DXd+Cap RP2D (n=7) showed ecacy with
this combination in heavily pretreated, trastuzumab- and uoropyrimi-
dine-refractory, HER2+ GC/GEJA. is study is ongoing.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organiser KUKM GmbH and KUKM
can disclose them if needed.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts94
1065
Perioperative epidural analgesia has no eect on survival
after partial pancreatoduodenectomy: long-term follow-up of
a multicenter randomized controlled trial
Rosa Klotz1; Maximilian Joos1; Anja Tremmel1; Christopher Büsch2;
Phillip Knebel1; Jan Larmann3
1Department of General, Visceral- and Transplantation surgery, Heidelberg
University Hospital, Heidelberg, Deutschland
2Institute of Medical Biometry, University of Heidelberg, Heidelberg,
Deutschland
3Department of Anesthesia, Heidelberg University Hospital, Heidelberg,
Deutschland
Background: Perioperative thoracic epidural analgesia (EDA) and
patient-controlled intravenous analgesia (PCIA) are frequently used for
pain management aer pancreatic surgery. e PAKMAN trial found that
the occurrence of postoperative gastrointestinal complications does not
dier between perioperative EDA and PCIA aer partial pancreatodu-
odenectomy (PD).1e purpose of the long-term follow-up (LTFU) of
this study is to compare the two analgesic strategies in terms of recur-
rence-free (RFS) and overall survival (OS).
Methods: e PAKMAN trial was a multicenter, randomized, controlled
superiority trial in which 124 patients with EDA were compared to 124
patients with PCIA aer PD. ree to ve years aer pPD a LTFU was per-
formed and OS, RFS and quality of life were assessed. OS was measured
from the date of pPD until the date of death or censored at last follow-up.
Survival curves were generated using the Kaplan–Meier method and com-
pared between the two intervention groups with the log-rank test.
Result: Data of 111 patients with PCIA and 111 patients with EDA were
available for LTFU. Analysis of OS revealed no signicant dierence
between both groups (p=0.39). Also, subgroup analysis including only
patients with malignant diseases revealed comparable OS.
Discussion: Recent observational studies have found an association
between use of regional anesthesia for cancer surgery and reductions in
disease recurrence. is potential benet of EDA could not be conrmed
in this LTFU of the multicenter randomized controlled PAKMAN trial.
Conclusion: is study found that the choice between PCIA and EDA
for pain control aer pancreatic surgery should not be based on concerns
regarding long-term survival.
Indication of source:
1. Klotz R et al. Gastrointestinal Complications Aer Pancreatoduodenectomy
With Epidural vs Patient-Controlled Intravenous Analgesia: A Randomized
Clinical Trial. JAMA Surg. 2020;155(7):e200794.
Disclosure Statement: e authors declare no conict of interest.
1074
Trastuzumab Deruxtecan (T-DXd) in Patients (Pts)
With HER2-Positive Gastric Cancer (GC) or Gastroesophageal
Junction (GEJ) Adenocarcinoma Who Have Progressed On or
After a Trastuzumab-Containing Regimen (DESTINY-Gastric04,
DG-04): A Randomized Phase 3 Study
Kohei Shitara1; Ferdous Barlaskar2; Fabio A. Franke3; Yoshinori
Kawaguchi2; Lin Shen4; Takahiro Kamio5; Gerold Meinhardt2;
Josep Tabernero6
1National Cancer Center Hospital, Tokyo, Japan
2Daiichi Sankyo, Basking Ridge, NJ, USA
3Hospital Unimed Noroeste, Ijuí, Brasilien
4Beijing Cancer Hospital, Beijing, China, VR
5Daiichi Sankyo, Tokyo, Japan
6Vall dHebron University Hospital, Barcelona, Spanien
Background: T-DXd is an antibody–drug conjugate of an anti-HER2
antibody, a cleavable tetrapeptide-based linker, and a topoisomerase I
inhibitor. T-DXd is approved globally to treat HER2+ metastatic breast
cancer, and in the US and Japan to treat advanced HER2+ GC. In the
primary analysis of DESTINY-Gastric01 (NCT03329690), an open-label,
multicenter, randomized, phase 2 trial in pts with HER2+ advanced GC/
GEJ carcinoma, T-DXd showed clinically relevant improvement vs. with
standard of care in objective response rate (ORR; 51% vs 14%; P < 0.001)
and overall survival (OS) benet (12.5 vs 8.4 mo; hazard ratio [HR] 0.59
[95% CI 0.39-0.88]; P = 0.01) in the 3L or later (Shitara, N Engl J Med
2020). e DG-04 study aims to evaluate the ecacy and safety of T-DXd
vs the combination of ramucirumab (ram) and paclitaxel (ptx) in pts with
HER2+ GC/GEJ carcinoma in the 2L setting.
Methods: DG-04 (NCT04704934) is a phase 3, global, multicenter, ran-
domized, open-label study. Eligible pts must be adults, with ECOG status
of 0 or 1, documented GC/GEJ carcinoma previously treated in the met-
astatic 1L setting with a trastuzumab (tmab)-containing regimen. HER2-
positivity (IHC3+ or IHC2+/ISH+) must be centrally conrmed on tumor
biopsies obtained aer progression on or aer tmab. Pts must not have
received anticancer therapy aer a rst-line tmab-containing regimen. Pts
will be randomized 1:1 to T-DXd (6.4 mg/kg every 3 weeks) or ram (8 mg/
kg on days 1 and 15 of a 28-day cycle) with ptx (80 mg/m2 on days 1, 8,
and 15 of a 28-day cycle). DG-04 is actively enrolling with approximately
490 participants planned. Primary endpoint is OS, secondary endpoints
include progression-free survival, ORR, duration of response, disease
control rate, safety, pharmacokinetics, and T-DXd immunogenicity.
Funding: Daiichi Sankyo, Inc., and AstraZeneca
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organiser KUKM GmbH and KUKM
can disclose them if needed.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 95
Genitourinary Cancer including Prostate Cancer
Best-of-Abstract-Vortrag
556
Clinical and histopathological characterization of penile
carcinomas with focus on HPV-status and histological subtype
Jan Mink1; Oybek Khalmurzaev2; Sebastian Hölters1; Alexey Pryalukhin3;
Julia Heinzelbecker1; Stefan Lohse4; Kristof Bende5; Hagen Loertzer6;
Joachim Steens7; Carmen Jerónimo8; Heiko Wunderlich9; Rainer Bohle3;
Michael Stöckle1; Vsevolod Matveev2; Arndt Hartmann5; Kerstin Junker1;
João Lobo8; Rui Henrique8
1Universitätsklinikum des Saarlandes, Abteilung für Urologie und
Kinderurologie, Homburg, Deutschland
2Federal State Budgetary InstitutionN.N. Blokhin National Medical Research
Center of Oncologyоf the Ministry of Health of the Russian Federation,
Department of Urology, Moscow, Russische Föderation
3Universitätsklinikum des Saarlandes, Abteilung für Pathologie, Homburg,
Deutschland
4Universitätsklinikum des Saarlandes, Abteilung für Virologie, Homburg,
Deutschland
5Universitätsklinikum Erlangen, Abteilung für Pathologie, Erlangen, Deutschland
6Westpfalz Klinikum Kaiserslautern, Abteilung für Urologie und Kinderurologie,
Kaiserslautern, Deutschland
7St.-Antonius-Hospital, Abteilung für Urologie und Kinderurologie, Eschweiler,
Deutschland
8Portuguese Oncology Institute of Porto, Porto Comprehensive Cancer Center
(Porto.CCC) & RISE@CI-IPOP (Health Research Network), Porto, Portugal
9St. Georg Klinikum Eisenach, Klinik für Urologie und Kinderurologie, Eisenach,
Deutschland
Background: Most data on prognostic factors for penile cancer (PC) are
based on small cohort sizes, and even meta-analyses are limited in patient
numbers. So in many situations there is a lack of evidence for clinical deci-
sions. About 50% of PC are HPV-associated, but there are conicting data
about the inuence of HPV-status on prognosis.
Methods: Clinical data and tissue samples from 276 patients with PC
from Germany, Russia and Portugal were collected. HPV-Status was
determined by genotyping and p16-immunostaining. Survival data were
analysed by Kaplan-Meier estimator, log rank test and uni- and multivar-
iate analysis using Cox regression model in relation to TNM stage, HPV
and histological subtype.
Result: In multivariate analysis, pN2-3 was signicantly associated with
worse cancer specic (CSS), metastasis free (MFS) and overall survival
(OS) (p = <0.001). Lymphovascular invasion (LVI) was an independent
prognostic parameter for worse CSS (p = 0.005) and OS (p = 0.007),
whereas MFS was signicantly dierent between pT1b and pT1a (p =
0.017). In pN0-patients, LVI was signicant for MFS (p = 0.032). Grading
and perineural invasion were signicant in univariate but not in multivar-
iate analysis. HPV-status was not associated with prognosis. Histological
subtypes dier in prognosis, without reaching statistical signicance.
Discussion: In accordance with literature lymphatic involvement had
the most signicant inuence on prognosis. So the poor prognosis in the
pT1b-group seems to be due to the inclusion of cases with LVI in this
group.
Conclusion: As LVI is a signicant independent prognostic parameter,
the inclusion of tumor-grade and LVI in a single T-category (pT1b) seems
questionable. Histological subtype should always be determined, whereas
HPV-status seems to be of minor clinical relevance. Nodal negative
patients with LVI are on a higher risk of metastasis. erefore, LVI should
be considered as an important factor in the decision making process aer
treatment of the primary tumor.
Disclosure Statement: e authors declare no conict of interest.
Poster
22
Hypoalbuminemia as a predictor of wound healing disorders
in inguinal lymphadenectomy in the context of penile
carcinoma
Desiree Louise Dräger1, Sophie Groh1, Tim Buchholz1, Oliver Hakenberg1
1Klinik und Poliklinik für Urologie, Universitätsmedizin Rostock, Rostock
Purpose: Inguinal lymphadenectomy is part of the operative management
of penile cancer from stage pT1b. e procedure is associated with wound
healing disorders that can delay the need for chemotherapy. Wound heal-
ing is a complex process that can be prevented by various factors. e
search for disruptive factors with subsequent elimination can, however,
become a successful treatment principle. We investigated hypoalbumin-
emia, as a marker of nutritional status, as a predictor of wound healing
disorders aer inguinal lymphadenectomy.
Material: Preoperative nutritional screening and collection of albumin,
which was correlated with postoperative wound healing disorders aer
inguinal lymphadenectomy in penile cancer patients (n = 89), taking into
account comorbidities, metastasis status and surgical technique.
Results: Wound healing disorders were associated with hypoalbuminemia
(<35 g/l; p = 0.006). Patients without malnutrition had signicantly fewer
postoperative complications (p<0.001). Multivariate analyzes showed that
hypoalbuminemia (p <0.0001), metastasis stage (p=0.004) and surgical
technique (p=0.011) were factors that were independently associated with
a poorer surgical outcome.
Discussion: Inguinal lymphadenectomy is part of the operative manage-
ment of penile cancer. Hypoalbuminemia and malnutrition can predict
impaired wound healing.
Conclusions: Nutritional conditioning prior to tumor surgery can have a
positive eect on the rate of postoperative complications.
Disclosure Statement: e authors declare no conict of interest.
29
Förderung von klinischen Studien in der Uro-Onkologie durch
die AUO
Heidrun Rexer; Peter Hammerer
Deutsche Krebsgesellschaft e. V., Arbeitsgemeinschaft Urologische Onkologie,
Berlin, Deutschland
Zielsetzung: Unterstützung für die Durchführung von qualitativ hoch-
wertigen Studien im Bereich der Uro-Onkologie.
Methoden: Die Arbeitsgemeinscha Urologische Onkologie (AUO)
der Deutschen Krebsgesellscha hat sich seit ihrer Gründung in
den 90er-Jahren zum Ziel gesetzt, die Durchführung von klinischen
Studien im Bereich der Uro-Onkologie zu fördern. Von Beginn an lag
das Augenmerk auf der hohen Qualität sowie der möglichst raschen
Durchführung der Studien, um die medizinische Versorgung uro-onkol-
ogischer Patienten zu verbessern.
Um hochwertige Studien zu identizieren, hat die AUO einen
Kurzbegutachtungsprozess entwickelt, mit dem die vorgelegten Studien
auf Sinnhaigkeit und Machbarkeit geprü werden. Bei positivem
Studienergebnis unterstützt die AUO die Studiendurchführung durch
verschiedene Maßnahmen, um eine möglichst rasche Rekrutierung
der Studie zu erreichen. Hierfür wird die jeweilige Studie auf der
AUO-Homepage präsentiert und durch Artikel der AUO in mehreren
Fachzeitschrien publiziert. Durch die so erreichte breite Leserscha
können wir die potentielle Zuweisung von geeigneten Patientinnen und
Patienten in die teilnehmenden Studienzentren verbessern.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts96
Ergebnisse/Status: Derzeit werden durch die AUO fast 40 Studien für
die Indikationen Urothelkarzinom, Prostatakarzinom, Hodenkarzinom
sowie Nierenzellkarzinom gefördert. Es wird ein Überblick über die
geförderten Studien gegeben.
Schlüsselwörter: Uro-Onkologie, klinische Studien, AUO
Korrespondenzadresse:
Heidrun Rexer
AUO
Seestr. 11, 17252 Schwarz
AUO@MeckEvidence.de
Disclosure Statement: e authors declare no conict of interest.
48
Contemporary physician-patient communication formats for
prostate and kidney cancer patients
Andreas Ihrig1
1Klinik für Allgemeine Innere Medizin und Psychosomatik, Universitätsklinik
Heidelberg, Sektion Psychoonkologie, Heidelberg, Deutschland
Background: Diagnostic processes of physicians are characterized by
guidelines and medical knowledge. Treatment decision-making processes
(TD-MP) of patients are oen unstructured and individually dierent.
erefore, the physician -patient conversation has a central importance
for the TD-MP of patients.
Methods: Current needs and experiences of renal and prostate cancer
patients (PCP) are examined in 3 studies in TD-MP and 3 studies exam-
ining contemporary approaches of physician-patient communication.
Result: PCP reported using Internet information and recommendations
from friends as a basis for their TD, in addition to recommendations from
physicians. Only 5.5% of 7169 PCP indicated that they wanted to leave
their TD predominantly to their physician. Participants of an Internet
self-help online forum were signicantly younger and the proportion of
relatives was signicantly higher than in traditional self-help groups. More
than 25% of patients reported that their therapy decision was signicantly
inuenced by the self-help group. Educational talks with multimedia sup-
port before prostatectomy were rated signicantly more positively than
classical talks. Patient participation in renal tumor boards was rated posi-
tively by both patients and physicians.
Discussion: We found patients to prefer a more active participation in
TD-MP compared to previous surveys. Information from the Internet
and recommendations from relatives seem to play an increasing role in
the TD-MP of patients. is information overload could lead to patients
being overwhelmed and including non-valid information in their TD-MP.
Patients might opt for a therapy that does not comply with the guidelines
without being aware of the medical background.
Conclusion: Multimedia elements are a contemporary addition to
the physician-patient conversation. For more complex medical issues,
patients should be given the opportunity to participate in tumor boards.
Experiencing the interdisciplinary exchange strengthens their condence
in the recommendation.
Disclosure Statement: e authors declare no conict of interest.
67
Sequential treatment patterns over time for advanced renal
cell carcinoma: data from the German research platform
CARAT
Peter J. Goebell1; Carsten Grüllich2; Lothar Müller3; Martin Bögemann4;
Uwe Martens5; Eyck von der Heyde6; Dietmar Reichert7; Arnd Nusch8;
Anke Schlenska-Lange9; Natalie Wetzel10; Michaela Koska10;
Martina Jänicke10; Norbert Marschner11; Michael Staehler12;
Viktor Grünwald13
1Universitätsklinikum Erlangen, Kinderurologie, Urologie, Erlangen, Deutschland
2Universitätsklinikum Carl Gustav Carus Dresden, Urologie, Dresden,
Deutschland
3Onkologie UnterEms Leer-Emden-Papenburg, Dr. L. Müller, Leer, Deutschland
4Universitätsklinikum Münster, Urologie und Kinderurologie, Münster,
Deutschland
5SLK Kliniken Heilbronn, Klinik für Innere Medizin III, Heilbronn, Deutschland
6Onkologische Schwerpunktpraxis, Hannover, Deutschland
7Gemeinschaftspraxis für Hämatologie und Onkologie, Westerstede,
Deutschland
8Praxis für Hämatologie und internistische Onkologie, Ratingen, Deutschland
9Krankenhaus Barmherzige Brüder, Onkologie und Hämatologie, Regensburg,
Deutschland
10iOMEDICO, Freiburg, Deutschland
11Praxis für interdisziplinäre Onkologie & Hämatologie, Freiburg, Deutschland
12Klinikum der Universität München Campus Großhadern, Urologische Klinik
und Poliklinik, München, Deutschland
13Universitätsklinikum Essen (AöR), Innere Klinik, Tumorforschung, Essen,
Deutschland
Background: Multiple novel treatments options have emerged for
advanced renal cell carcinoma (mRCC) including several tyrosine kinase
inhibitors (TKIs), mTOR inhibitors (mTOR), and checkpoint-inhibitors
(CPIs). Here, we analysed changes in sequential treatment patterns over
time since 2008.
Methods: CARAT (NCT03374267) is a prospective, observational, clin-
ical registry, which continues the preceding Tumor Registry Renal Cell
Carcinoma (RCC Registry) in Germany. By April 2022, 2290 patients
(pts) in total have been enrolled with 800 pts since the start of CARAT in
2017. Pts are recruited at start of 1st-line treatment, independent of their
treatment. Details on treatments, patient and tumour characteristics and
patient-reported outcomes are collected. Follow-Up is until death or up to
3 years. For the analyses reported herein, all pts with at least one year of
follow-up (N=1717, start of treatment prior to 31/12/2020, database cut
31/12/2021) were considered.
Result: Of 1717 pts, 50% started a 2nd-line treatment, while 26% died
during 1st-line treatment. For 16% 1st-line treatment was ongoing, 8%
were lost to follow-up.
Pts who died prior to 2nd-line treatment were older (median 72 vs. 68
years) and more oen had poor risk IMDC score (40% vs. 17%) and/or
comorbidities (Charlson-Comorbidity-Index ≥1 41% vs. 31%). At the
time of analysis, 75% of pts with start of treatment since 2018 were alive.
Most frequently used 1st-line strategies have changed from mostly TKI to
both, TKI-only or CPI-based treatments. Up to 2014 the most frequent
1st-2nd-line strategies were TKI-mTORi or TKI-TKI (each 19%). 2015-
2018, the sequence TKI-CPI became more frequent (29%) than TKI-TKI
(12%). In 2020 the most common strategies were CPI or CPI+TKI in
1st- and TKI in 2nd-line therapy (7 or 6%) or TKI in 1st-line and CPI in
2nd-line therapy (5%).
Conclusion: Sequential treatments of pts with mRCC are changing show-
ing that novel treatment options are quickly implemented into routine
care in Germany. With longer follow-up, we will provide valuable addi-
tional evidence to guide treatment strategies in the future.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 97
82
Cabozantinib in adult patients with advanced renal cell
carcinoma following prior systemic checkpoint inhibition
therapy: a retrospective, non-interventional study
Viktor Grünwald1; Martin Bögemann2; Reza Rafyian3; Günter Niegisch4;
Marco Schnabel5; Anne Flörcken6; Michael Maasberg7; Christoph Maintz8;
M.-O. Zahn9; Anke Wortmann10; Andreas Hinkel11; Jochen Casper12;
Christopher Darr13; Thomas Hilser1; Matthias Schulze14; Disorn Sookthai15;
Caroline Schönherr15; Philipp Ivanyi16
1Universitätsklinikum Essen (AöR), Westdeutsches Tumorzentrum Essen, Innere
Klinik (Tumorforschung), Essen, Deutschland
2Universitätsklinikum Münster, Klinik für Urologie und Kinderurologie, Müster,
Deutschland
3Krankenhaus Nordwest gGmbH, Institut für Klinisch-Onkologische Forschung
(IKF), Frankfurt, Deutschland
4Universitätsklinikum Düsseldorf, Klinik für Urologie, Konservative Urologische
Onkologie, Düsseldorf, Deutschland
5Klinik für Urologie der Universität Regensburg am Caritas-Krankenhaus St.
Josef, Regensburg, Deutschland
6Medizinische Klinik m.S. Hämatologie, Onkologie und Tumorimmunologie,
Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin,
Deutschland
7Institut für Versorgungsforschung, Mayen, Deutschland
8MVZ West GmbH Würselen, Würselen, Deutschland
9MVZ Onkologische Kooperation Harz, Goslar, Deutschland
10Onkologiezentrum Soest-Iserlohn, Medizinisches Versorgungszentrum GbR,
Soest-Paradiese, Deutschland
11Franziskus Hospital Bielefeld, Onkologisches Zentrum, Bielefeld, Deutschland
12Klinikum Oldenburg AöR, Universitätsklinik für Innere Medizin - Onkologie und
Hämatologie, , Oldenburg, Deutschland
13Universitätsklinikum Essen Klinik für Urologie, Essen, Deutschland
14Praxis Dr. Schulze, Markkleeberg, Deutschland
15Institut für Klinische Krebsforschung IKF GmbH, Frankfurt, Deutschland
16Medizinisch Hochschule Hannover, Klinik für Hämatologie, Hämostaseologie,
Onkologie und Stammzelltransplantation, Hannover, Deutschland
Background: With the current 1st line shi towards IO-combinations, e-
cacy and safety data of subsequent therapies remains scarce. Cabozantinib
is a standard of care, but data aer IO-failure remains anecdotal. erefore,
primary aim was to evaluate safety and eectiveness of cabozantinib aer
failure of IO-based therapies.
Methods: Data was collected retrospectively from sites in Germany.
Patients (pts) with advanced or metastatic renal cell carcinoma (mRCC)
were eligible. Cabozantinib treatment directly aer failure of IO-based
therapy was mandatory. AEs were reported according to CTCAE 5.0.
Objective response rate according to RECIST 1.1 and Progression Free
Survival (PFS) were collected from medical records. Descriptive statistics
and KM-plots were utilized, where appropriate.
Result: is preliminary analysis (cut o 30-Apr-21) assessed 56 eligible
pts (71.4% male) with median age of 66 yrs. Clear cell RCC was reported
in 66.1% (n=37) and nephrectomy in 87.5% (n=49). 87.5% (n=49) had
≥2 previous lines. ECOG ≤1 was 32.1% (n=18). IMDC factors were 0 in 3
(5.4%), ≥1 in 20 (35.7%), missing in 33 pts (58.9%). 62.5% (n=35) started
at reduced dose. 53.6% (n=30) required dose reductions, 7.1% (n=4)
interruptions and 14.3% (n=8) discontinuation of cabozantinib. PR was
reported in 10.7% (n=6), SD in 19.6% (n=11), PD in 12.5% (n=7) and
missing in 57.1% (n=32). Median treatment duration was 5.9 months and
median PFS was 6.64 months (95% CI 4.99, 8.71). AEs were reported in
87.5% (n=49) and 42.9% (n=24) had grade 3-5. Fatigue (33.3%), diarrhea
(31.7%) and hand-foot-syndrome (23.3%) were the 3 most frequent AEs
of any grade and causality. SAE were reported in 21.4% (n=12), 2 were
fatal.
Discussion: Cabozantinib followed directly aer IO therapy was tolerated
and feasible. No new safety signals were reported. A lower starting dose
was frequently utilized in this real-world cohort of RCC pts but was asso-
ciated with a favorable tolerability prole.
Conclusion: Our data supports the use of cabozantinib aer IO-failure.
Major limitation was the retrospective data capture in our study.
Disclosure Statement: e authors declare no conict of interest.
101
Primary radio(chemo)therapy for inoperable muscle-invasive
bladder cancer – long term results and patterns of care in a
single institution
Laura Anna Fischer1; Leif Hendrik Dröge1; Sandra Donath1;
Stephanie Bendrich1; Jacqueline Possiel1; Markus Schirmer1; Martin Leu1;
Manuel Guhlich1; Andrea Hille1; Stefan Rieken1; Rami El Shae1
1Universitätsmedizin Göttingen, Klinik für Strahlentherapie und Radioonkologie,
Göttingen, Deutschland
Background: Radical cystectomy (RC) is the standard of care for mus-
cle-invasive bladder cancer (MIBC). In selected patients, bladder-sparing
trimodal therapy (TMT) can be considered as an alternative treatment,
potentially improving quality of life.
Methods: Between 1998 and 2021, 66 patients received denitive radio-
therapy for inoperable bladder cancer at the University Medical Center
Göttingen. Normofractionated external beam radiotherapy was delivered
at a median total dose of 50,4 Gy (Q1–Q3: 50,3–50,4 Gy) to the blad-
der, including limited pelvic lymph nodes in 40 (87%) cases. A sequential
boost to the primary was delivered at a median total dose of 55,8 Gy (Q1-
Q3: 55,8–59,4 Gy).
Following ethics committee approval, data was retrieved from the patients
medical and legal records. Patient characteristics, disease prole, treat-
ment pattern, response and OS are analyzed by the methods of Kaplan-
Meyer and log-rank test.
Results: Median patient age was 79,5 years (Q1–Q3: 69,25–84 years).
Of 72 patients, 46 were treated with curative intent, 44 patients under-
went transurethral resection of bladder tumor followed by radiation,
18 patients received a concurrent radiosensitizing chemotherapy (plati-
num-based (n=17) or mitomycin C plus 5-uorouracil (n=1)). Treatment
was discontinued in 5 patients due to a tumor associated deterioration
of general condition, one patient died. Long-term follow-up showed a
decline in bladder function in 43% (e.g. dysurea, pollakisurea), 15% had
an inoperative bladder, only one patient underwent a salvage cystectomy.
2- and 5-year overall survival rates were 59% and 29%, in the TMT sub-
group 75% and 43%.
Conclusion: Radio(chemo)therapy for the treatment of bladder cancer is
safe and feasible and potentially benecial, especially for elderly patients
regarding bladder preservation and avoidance of morbidity or mortality
of RC.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts98
128
Thrombospondin-2 and LDH: potential predictive biomarkers
for the treatment of metastatic renal cell carcinoma
with everolimus after one VEGF-targeted therapy
(MARC-2 study)
Philip Zeuschner1; Sebastian Hölters1,2; Michael Stöckle1; Barbara Seliger3;
Anja Müller3; Hagen S Bachmann4; Viktor Grünwald5,6; Daniel C
Christoph7,8; Arnulf Stenzl9; Marc-Oliver Grimm10; Fabian Brüning11;
PeterJ. Goebell12; Marinela Augustin13; Frederik Roos14,15; Johanna Harde16;
Iris Benz-Rüd16; Michael Stähler17; Kerstin Junker1
1Saarland University, Department of Urology and Paediatric Urology, Homburg/
Saar, Deutschland
2Ingenieurbüro für Gesundheitswesen GmbH, Leipzig, Deutschland
3Insitute of Medical Immunology, Martin Luther University Halle-Wittenberg,
Halle (Saale), Deutschland
4Institute of Pharmacology and Toxicology, Center for Biomedical Education
an Research (ZBAF), School of Medicine, Faculty of Health, Witten/Herdecke
University, Witten, Deutschland
5University Hospital Hannover Medical School , Department of Hematology,
Hemostasis, Oncology and Stem Cell Transplantation, Hannover, Deutschland
6University Hospital Essen, West German Cancer Center, Clinic for Internal
Medicine (Tumor Research) and Clinic for Urology, Essen, Deutschland
7University Hospital Essen, Department of Medical Oncology, Essen,
Deutschland
8Evangelische Kliniken Essen-Mitte, Evangelische Huyssens-Stiftung Essen-
Huttrop, Department of Medical Oncology & Hematology, Essen, Deutschland
9University Hospital Tübingen, Department of Urology, Tübingen, Deutschland
10University Hospital Jena, Department of Urology, Jena, Deutschland
11Philipps-University Marburg, University Hospital Giessen and Marburg GmbH,
Department of Urology and Pediatric Urology, Marburg, Deutschland
12University Hospital Erlangen, Ambulatory Uro-Oncological Therapy Unit
Erlangen (AURONTE), Department of URology and Clinic for Haematology and
Internistic Oncology, Erlangen, Deutschland
13Klinikum Nuremberg, Paracelsus Medical University, Department of
Hematology and Oncology, Nürnberg, Deutschland
14University Medical Center Mainz, Departmet of Urology and Paediatric
Urology, Mainz, Deutschland
15University Hospital Frankfurt, Department of Urology, Frankfurt, Deutschland
16iOMEDICO, Medical Department, Freiburg im Breisgau, Deutschland
17Ludwig-Maximilians-University of Munich, Department of Urology,
Interdisciplinary Center of Renal Tumors, München, Deutschland
Background: e phase IV MARC-2 trial searched for predictive blood
biomarkers in patients with clear cell metastatic renal cell carcinoma
(mRCC) treated with everolimus 2nd line. In an exploratory approach,
the relation of potential biomarkers to clinical endpoints was assessed.
Methods: e expression of 55 angiogenesis-related proteins at C1D1 and
C1D15 were screened by antibody arrays and validated by ELISA in 63
patients. ree metabolic molecules and 4 SNPs in the mTOR gene were
analyzed. Cut-os were calculated with ROC analysis, the survival was
assessed with Kaplan Meier curves and multiple Cox regressions.
Result: Lower levels of angiogenesis-related protein thrombospon-
din-2 (TSP-2) at baseline (≤ 665 parts per billion, ppb) identied ther-
apy responders with longer median progression-free survival (PFS, 6.9
months vs. 1.8, p=0.005). Two weeks aer treatment initiation, responders
had higher LDH (>27.14nmol/l) associated with longer median PFS (3.8
mo vs. 2, p=0.013) and overall survival (OS, 31.0 mo vs. 14.0, p<0.001).
Baseline TSP-2 levels were a stronger independent baseline predictor for
PFS (HR 0.22, p=0.001) than patient characteristics. mTOR polymor-
phisms had a tendency to be associated with therapy response, but were
not signicant.
Discussion: Especially in 2nd and later treatment lines in mRCC, choosing
the optimal drug for each patient remains an unsolved challenge. Blood
biomarkers could serve as minimally-invasive predictive or on-treatment
indicators, whether to continue or change the regimen.
Conclusion: Low baseline thrombospondin-2 and high lactate dehydro-
genase two weeks aer therapy initiation identied patients with longtime
responses to everolimus, which could further increase the response rates
based on individual patient selection.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
149
Episensitation of Cisplatin-Resistant and Naïve Urothelial
Carcinoma Cells towards PARP Inhibitor Treatment
by BET-Inhibitor PLX51107
Anna L. Bartkowiak1; Leandra Lepping1; Sophia Thy1; Sarah Meneceur1;
Patrick Petzsch2; Karl Köhrer2; Michèle Homann1; Günter Niegisch1
1Klinik für Urologie, Heinrich-Heine-Universität Düsseldorf, Medical Faculty,
Düsseldorf, Deutschland
2Biologisch-Medizinisches Forschungszentrum (BMFZ), Heinrich-Heine-
Universität Düsseldorf, Medical Faculty, Düsseldorf, Deutschland
Background: Since muscle-invasive urothelial carcinoma (UC) frequently
develop cisplatin resistance new therapeutic options are urgently needed.
Previously, we reported about the bromodomain protein inhibitor (BETi)
PLX51107 (PLX) inducing DNA damage and repair (DDR) deciency
in UC cell lines (UCC), a state also called BRCAness, that is sensitive to
PARP inhibition in other entities. Since Cisplatin-resistant sublines of
UCC (LTTs) are highly dependent on DDR and apoptosis resistance, we
characterized response of LTTs and treatment naïve parental cells towards
combined treatment with PLX51107 and the PARP inhibitor (PARPi)
Olaparib.
Methods: Transcriptomic changes by PLX treatment were detected by
RNA sequencing of two UCC (VM-CUB1 and UM-UC-3) and the benign
control cell line HBLAK. Dierentially expressed genes regulating DDR
and apoptosis were further analysed in transcriptomic proles of three
dierent LTT sublines (RT-112, T-24, J82) compared to their parent cell
lines. Treatment response towards PLX and PARPi Olaparib mono treat-
ment as well as the combination was investigated in named UCC and
HBLAK by MTT assay.
Results: Induction of DDR deciency by PLX and altered expression of
apoptosis regulators was conrmed by qRT-PCR. Factors that may deter-
mine treatment response of UC cells towards BETi and PARPi were iden-
tied. Combination treatment was highly synergistic in LTTs and parental
cell lines, allowing extensive dose reduction. Synergistic eects were con-
rmed by ow cytometry (apoptosis) and clonogenic assays. Combination
of the PARPi with Cisplatin instead of the BETi did not exert synergistic
eects in cisplatin resistant cells.
Discussion: Synergistic treatment with the BETi PLX51107 and the
PARPi Olaparib strongly reduced viability of cisplatin-resistant and –sen-
sitive UCC, but spared normal cells.
Conclusion: Applicability of PARPi may be extended to BRCA wild-type
cancer patients by episensitation with PLX51107. us, this combination
could be a promising therapeutic option for UC also for second line treat-
ment aer chemotherapy.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 99
151
Role of prior nephrectomy for synchronous metastatic renal
cell carcinoma (mRCC) on ecacy in patients treated with
avelumab + axitinib (A + Ax) or sunitinib (S): results
from JAVELIN Renal 101
Marc-Oliver Grimm1; Mototsugu Oya2; Toni K Choueiri3;
Manuela Schmidinger4; David Quinn5; Gwenaelle Gravis-Mescam6;
Elena Verzoni7; Alfonsus Van den Eertwegh8; Alessandra DI Pietro9;
Mariangela Mariani9; Jing Wang10; Despina Thomaidou11;
Laurence Albiges12
1Universitätsklinikum Jena - Klinikum Lobeda, Jena, Deutschland
2Keio University School of Medicine, Tokyo, Japan
3Dana-Farber Cancer Institute, Boston, USA
4Medical University of Vienna, Vienna, Österreich
5Keck School of Medicine USC, Los Angeles, USA
6Institute Paoli-Calmettes, Marseille, Frankreich
7Istituto Nazionale dei Tumori | Fondazione IRCCS, Milano, Italien
8VU University Medical Center, Amsterdam, Niederlande
9Pzer SRL, Milan, Italien
10Pzer, Cambridge, USA
11Pzer, Athens, Griechenland
12Gustave Roussy Cancer Campus, Villejuif, Frankreich
Background: Cytoreductive nephrectomy (neph) remains controversial
in the management of mRCC; the role of neph before immune checkpoint
inhibitor treatment is unknown. In this follow-up analysis of the phase 3
JAVELIN Renal 101 trial (NCT02684006), we assessed the role of prior
neph in patients (pts) with mRCC with synchronous metastases at diag-
nosis treated with A + Ax or S.
Methods: Ecacy outcomes were assessed from the third interim analysis
in pts with mRCC who had M1 disease at diagnosis and had prior neph
or no neph in the A + Ax and S arms. Multivariate Cox regression analy-
ses were used to assess hazard ratios (HRs) for overall survival (OS) and
progression-free survival (PFS; investigator assessment per RECIST 1.1).
Logistic regression was used to obtain odds ratios for objective response
(OR; investigator assessment per RECIST 1.1).
Results: 412 of 886 pts in JAVELIN Renal 101 had M1 disease at diagnosis,
of which 126 (A + Ax) and 147 (S) had prior neph, and 72 (A + Ax) and 67
(S) had no neph. A higher proportion of pts in the no neph vs prior neph
group were older (42% vs 32% were ≥65 years), had impaired PS (ECOG
PS 1, 54% vs 40%), and had poor prognosis (40% vs 16% by IMDC cri-
teria); fewer pts had PD-L1+ tumors (40% vs 77%). To assess the impact
of prior neph, these parameters were adjusted in the multivariate model.
Post hoc analyses showed that in the A + Ax arm, observed PFS and OS
were numerically improved in the prior neph vs no neph group (PFS, HR
[95% CI] 0.785 [0.531-1.161]; OS, HR 0.593 [0.379-0.930]); however, no
dierences were observed in the S arm (PFS, HR 1.146 [0.773-1.699]; OS,
HR 0.859 [0.551-1.341]. Conrmed OR was numerically longer in pts
with neph vs no neph in the A + Ax arm (odds ratio 2.669 [1.315-5.414])
but not in the S arm (odds ratio 2.018 [0.824-4.941]).
Discussion/Conclusions: Pts who had M1 disease at diagnosis and prior
neph had numerically improved ecacy outcomes vs no neph with A +
Ax but not with S.
Previously presented at ESMO 2021, “FPN: 665P”, “Marc O. Grimm etal.
- Reused with permission
Disclosure Statement: e disclosures are included in the abstract document
152
Final results on ecacy and patient reported outcomes (PRO)
of a randomized phase II trial investigating nivolumab
switch-maintenance after TKI induction in metastatic
clear cell renal cell carcinoma (mRCC) patients (NIVOSWITCH)
Christopher Darr1; Stefanie Zschäbitz2; Philipp Ivanyi3; Manfred Wirth4;
Peter Staib5; Martin Schostak6; Lothar Müller7; Michael Metz8;
Lothar Bergmann9; Thomas Steiner10; Anja Lorch11; Philipp Schütt12;
Mohammad-Reze Rayan13; Eva Hellmis14; Axel Hinke15; Martin Mänz16;
Johannes Meiler17; Thomas Kretz18; Anne Flörcken19; Viktor Grünwald20
1Klinik für Urologie, Universitätsmedizin Essen, Essen, Deutschland
2Klinik für Medizinische Onkologie, Universitätsklinikum Heidelberg,
Deutschland
3Medizinische Hochschule Hannover (MHH) Klinik für Hämatologie,
Hämostaseologie, Onkologie und Stammzelltransplantation, Hannover,
Deutschland
4Klinik für Urologie, Universitätsklinikum Dresden
5Klinik für Hämatologie und Onkologie, St. Antonius Hospital Eschweiler
6Klinik für Urologie, Universitätsklinikum Magdeburg
7Onkologie Untere Ems
8Gemeinschaftspraxis Hämatologie / Onkologie , Göttingen
9Hämatologie / Onkologie, Frankfurt am Main, Deutschland
10Klinik für Urologie, Helios Klinikum Erfurt
11Klinik für Medizinische Onkologie und Hämatologie, Universitätsspital Zürich
12Onkologische Gemeinschaftspraxis Gütersloh
13Klinik für Onkologie und Hämatologie, Krankenhaus Nordwest, Frankfurt
14Urologicum Duisburg, Duisburg
15Cancer Clinical Research Consulting, Düsseldorf
16Clinical Oncology Resources Berlin GmbH, Berlin
17Hämatologie / Onkologie, Klinik Dr. Hancken
18Urologie Heinsberg
19Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und
Tumorimmunologie, Charite Universitätsmedizin Berlin
20Klinik für Urologie und Innere Klinik Tumorforschung, Universitätsklinik Essen
Background: In mRCC patients (pts) combinations of checkpoint inhib-
itors (CPI) and tyrosine kinase inhibitors (TKI) are considered standards
of care. Our study investigated a 1st line switch-maintenance approach
(CPI aer TKI) to improve outcome in mRCC.
Methods: 49 pts. with partial remission (PR) or stable disease (SD) aer
12 weeks TKI induction therapy were 1:1 randomized to receive either
TKI continuation (24 pts.) or nivolumab (NIVO; 25 pts.; 240 or 480 mg
IV q2-4wk). Data base was closed 12/2020. Pts. with ECOG 0-2 and ade-
quate organ function were permitted. Objective response rate (ORR), pro-
gression free survival (PFS) and adverse events (AE, according to CTCAE
v4.03) were assessed from time of randomization. PRO were assessed by
the FACT Kidney Symptom Index (FKSI-15), with Time to deterioration
(TTD) dened as time between randomization to PRO decrease ≥3 points.
Result: Median age was 65 years, 82% were male and 4% had ECOG
2. Main metastatic sites were lung (47%), lymph nodes (27%) and liver
(24%). Response to TKI induction therapy was PR in 59% and SD in 41%
of pts. PFS was 3.0 vs. 11.9 mo. (HR = 2.57 [95% CI: 1.36 – 4.89]) in favor
for TKI continuation. e median OS was not reached. 2-year OS was
64% for NIVO and 66% for TKI treatment (HR = 1.12 [95% CI: 0.43 –
2.89]; P=0.82). ORR from randomization favored TKI continuation (16
vs. 48%; P=0.03). Aer a median follow-up of 26.3 mo (1.3-45.6), 40 PFS
events and 17 deaths occurred. AEs for NIVO vs. TKI occurred in 96% vs.
100%, grade 3-5: 56% vs. 71% and serious AE: 48% vs. 50%, respectively.
Median FKSI15 score showed no dierence, 46 and 47 for NIVO as well
as for TKI with 42 and 43. Median TTD favored NIVO (NR) vs. TKI (6.9
mo), but dierence remained insignicant (P=0.16).
Discussion: Although a lower degree of grade ≥3 AEs for NIVO was
observed, a PRO benet was not detected. A major limitation is the small
sample size and the selection of TKI-sensitive pts.
Conclusion: Our data do not support the use of a switch-maintenance
approach in mRCC.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts100
153
A prospective, open-label, multicenter, randomized phase
II trial: Sequential therapy with BEvacizumab, RAd001
(Everolimus) and AxiTinib in metastatic renal cell carcinoma
(mRCC) (BERAT study of the IAG-N)
Thomas Hilser1; Viktor Grünwald1; Lothar Bergmann2; Peter J. Goebell3;
Arne Strauß4; Johannes Meiler5; Arndt Hartmann6; Philipp Ivanyi7;
Jens Bedke8
1Universitätsklinikum Essen, Westdeutsches Tumorzentrum, Innere Klinik
(Tumorforschung), Essen, Deutschland
2Universitätsklinikum Frankfurt, Med. Klinik II für Hämatologie/ Onkologie,
Frankfurt am Main, Deutschland
3Universitätsklinikum Erlangen, Klinik für Urologie, Erlangen, Deutschland
4Universitätsmedizin Göttingen, Klinik für Urologie, Göttingen, Deutschland
5Klinik Dr. Hancken GmbH, Stade, Deutschland
6Universitätsklinikum Erlangen, Pathologisches Institut, Erlangen, Deutschland
7Medizinische Hochschule Hannover, Klinik für Hämatologie, Hämostaseologie,
Onkologie und Stammzelltransplantation, Hannover, Deutschland
8Universitätsklinikum Tübingen, Klinik für Urologie, Tübingen, Deutschland
Background: Inhibitors of the vascular endothelial growth factor or its
receptor (TKI) and mammalian target of rapamycin (mTORi) are com-
ponents of the targeted treatment landscape in mRCC. We compared the
2nd line ecacy of TKI and mTORi in mRCC aer failure of bevacizumab/
interferon in a phase II trial.
Methods: Key inclusion criteria were: measurable mRCC , ECOG 0-1,
IMDC risk: good or intermediate, adequate organ function. Patients who
progressed on or were intolerant to BEV/IFN were subject for random-
ization between VEGFRi and everolimus (EVE) treatment. Cross-over
occurred at time of progression during 2nd line treatment. Improvement
of 2nd line PFS-rate at 6 mo. from 50% to 65% was the primary endpoint.
Secondary endpoints were PFS, total PFS, ORR, OS, safety and HR-QoL.
Result: A total of 22 of 100 patients were included between Novmeber
2012 and June 2015 and at that time stopped for poor accrual. 10 patients
(46%) were randomized to receive 2nd line treatment with everolimus
(n=5) or Axitinib (n=4)/ Sunitinib (n=1). Objective response rate was
20% under 1st line treatment with Bev/IFN. Severe adverse events (SAE)
occurred in 60% each arm. ORR was 1/5 (20%) for TKI and 0/5 (0%) for
Everolimus. PFS rate at 6 mo. was 20 % in each arm. Median PFS was 3.7
mo. (EVE) and 2.2 mo. (VEGFRi) [HR 1.0 (95%-CI: 0.26-3.85; p=0.997)].
e OS was comparable between arms HR 1.12 (95%-CI: 0.27-4.61; p=
0.872). e HR-Qol was comparable between arms, too. e data will be
shown. 7 patients crossed over to 3rd line treatment.
Discussion: e rapid change of the treatment landscape, the limited use
of BEV/IFN in 1st line and the duration of 1st line treatment jeopardized
BERAT trial recruitment. e small number of patients is a major limita-
tion of our trial. Our observation indicated the principle poor prognosis
in progressive patients and the limited ecacy of axitinib, sunitinib or
everolimus in 2nd line treatment. Clearly, more ecient 2nd line therapies
are needed.
Conclusion: No major dierences for PFS rates at 6 mo. were detected,
indicating the limited activity of EVE or tested TKIs in 2nd line.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
158
An ongoing, randomized phase II study of Nivolumab
plus Ipilimumab versus standard of care in previously
untreated and advanced non-clear cell renal cell carcinoma
(SUNIFORECAST)
Marit Ahrens1; Bernard Escudier2; John Haanen3; Ekaterini Boleti4;
Marine Gross-Goupil5; Marc-Oliver Grimm6; Sylvie Negrier7;
Philippe Barthélémy8; Gwenaelle Gravis9; Philipp Ivanyi10; Jens Bedke11;
Daniel Castellano12; Andrej Panic13; Begona Mellado14; Pablo Maroto15;
Sylvie Rottey16; Stefanie Zschäbitz17; Anne Flörcken18; Martin Bögemann19;
Tom Waddell20; Cristina Suárez Rodríguez21; Anja Lorch22;
Dorothee Deckbar23; Arndt Hartmann24; Lothar Bergmann1
1University Hospital Frankfurt, Medical Clinic II, Hematology and Oncology,
Frankfurt, Deutschland
2Institut Gustave Roussy, Paris, Frankreich
3Netherlands Cancer Institute, Amsterdam, Niederlande
4Royal Free London NHS Foundation Trust, London, Vereinigtes Königreich
5Cente Hospitalier Universitaire, Bordeaux, Frankreich
6University Hospital Jena, Clinic for Urology, Jena, Deutschland
7Centre Leon Berard, Lyon, Frankreich
8Les Hôpitaux Universitaire de Strasbourg, Strasbourg, Frankreich
9Institut Paoli Calmettes, Clinic for Oncology, Marseille, Frankreich
10Hanover Medical School, Comprehensive Cancer Center Lower Saxony,
Department of Hematology, Hemostasis, Oncology and Stem Cell
Transplantation, Hannover, Deutschland
11University Hospital Tübingen, Clinic for Urology, Tübingen, Deutschland
12Hospital Universitario 12 de Octubre, Clinic of Oncology, Madrid, Spanien
13University Hospital Essen, Northwest German Cancer Center, Clinic for Urology,
Essen, Deutschland
14Hospital Clinic de Barcelona, Clinic for Oncology, Barcelona, Spanien
15San Pau Hospital, Barcelona, Spanien
16University Hospital, Gent, Belgien
17University Hospital Heidelberg, National Center for Cancer (NCT), Clinic for
Oncology, Heidelberg, Deutschland
18Charité Berlin, Berlin (Campus Virchow-Klinikum), Medical Clinic for
Hematology/Oncology and Tumorimmunology, Berlin, Deutschland
19University Hospital Münster, Clinic for Urology, Münster, Deutschland
20Christie NHS Foundation Trust, Manchester, Vereinigtes Königreich
21Hospital Universitari Vall dHebron, Vall dHebron Barcelona Hospital Campus,
Medical Oncology, Vall dHebron Institut of Oncology (VHIO), Barcelona, Spanien
22University Hospital Düsseldorf, Clinic for Oncology, Düsseldorf, Deutschland
23University Hospital Frankfurt, Frankfurt, Deutschland
24Institute for Pathology, University Hospital Erlangen, Erlangen, Deutschland
Background: e heterogenous group of non-clear cell renal cell carci-
nomas (nccRCC) accounts for approximately 25% of RCC patients (pts).
Data on treatment strategies are still limited, since most clinical trials focus
on clear-cell RCC. Recently dierent combination therapies with immune
checkpoint inhibitors (IO) and tyrosine kinase inhibitors (TKI) have
been approved for treatment in RCC independent of the International
Metastatic RCC Database Consortium (IMDC) risk group. In addition,
Nivolumab and Ipilimumab (IO/IO) has been approved for treatment
of intermediate and high-risk pts showing a signicant improvement in
overall response rate (ORR), progression free (PFS) and overall survival
(OS) compared to Sunitinib. Retrospective analysis and smaller trials have
shown promising results for IO-based therapies also in nccRCC pts.
Methods: SUNIFORECAST is an ongoing, randomized phase-II, multi-
center European trial including pts with advanced or metastatic nccRCC
without prior systemic therapy. Other key inclusion criteria are: avail-
able tumor tissue, Karnofsky >70% and measurable disease per RECIST
1.1. All histological diagnoses are reviewed by a central pathologist. e
study plans to randomize ~306 pts stratied for papillary or non-papil-
lary histology and by the IMDC risk score. Pts will be randomized 1:1 to
either i) Nivolumab 3mg/kg intravenously (IV) plus Ipilimumab 1mg/kg
IVevery 3 weeks for 4 doses followed by Nivolumab xed dose (FD)
240mg IV every 2 weeks (or 480mg IV every 4 weeks) or ii) Standard of
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 101
care according to the approved schedule. Treatment will be discontinued
in case of unacceptable toxicity or withdrawal of informed consent. Pts
may continue treatment beyond progression under certain circumstances.
Primary endpoint is the OS rate at 12 months. Secondary endpoints
include OS rate at 6 and 18 months, median OS, PFS, ORR and quality of
life. e trial is in progress and 260 patients (161 pts with papillary, 96 pts
with non-papillary histology) have been enrolled until now. Clinical trial
identication NCT03075423
Disclosure Statement: e authors declare no conict of interest.
195
The in vitro activity of Cabozantinib as rst- and second-line
agent in metastatic renal cell carcinoma
Angela Zaccagnino1; Bozhena Vynnytska-Myronovska2; Michael Stöckle3;
Kerstin Junker1
1Saarland University, Department of Urology and Pediatric Urology, Homburg,
Deutschland
2University of Saarland, D
3Saarland University, Department of Urology and Pediatric Urology
Background: Cabozantinib (Cbz), a MET/AXL/VEGFR inhibitor, showed
clinical benets as rst and second-line agent in mRCC. We tested the
molecular and cellular eects of Cbz in treatment naïve cells as well as
aer a chronic treatment with Sunitinib (Sun) in vitro.
Methods: e response to Cbz was tested by the IC50 method in the Sun-
resistant cells, 786-O/S and Caki-2/S, and the matching 786-O/WT and
Caki-2/WT. Immune blotting was used to study the signaling pathways.
Result: e 786-O/WT cells showed an IC50 of 10.8µM, while Caki-2/WT
13.6µM. In 786-O/WT, Cbz caused a late onset of the activated receptor
pMET (FC: -2.2) along with, the coupled proteins, Src and STAT3, and
impaired FAK. Under the same settings, pMET was completely inhibited
in Caki-2/WT cells (FC: -10.4). We saw a compensatory activation of FAK
and mTOR marker S6 within 24 h of treatment. As second-line drug, Cbz
had lower ecacy in 786-O/S cells (IC50 of 13µM, p- value 0.02 versus
WT), while no change was observed in Caki-2/S (IC50 of 12.6µM). e
Sun-pretreatment enhanced pMET only in 786-O/S. Following Cbz appli-
cation, the late inhibition of pMET (72 hs) was compensated by the boost
of Src and STAT3 in 786-O/S. In contrast, Cbz impaired pMET thoroughly
in Caki-2/S. In the Sun-pretreated cells, the baseline activation of FAK was
not aected by Cbz. Yet, the Sun-chronic treatment sensitized the resis-
tant cells to the inhibition of mTOR. Finally, the anti-apoptotic protein
Bcl-2 was enhanced at the maximum inhibition of MET, in 786-O/S and
Caki-2/WT.
Discussion: e pMET-driven status in the 786-O/S, Caki-2/WT and
Caki-2/S cells did not sensitize the cells towards Cbz. Aer MET inhi-
bition, the activation of Src-FAK protein axis and Bcl-2 might suggest a
synergy that could weaken Cbzs antitumor activity.
Conclusion: Our data suggest that pretreatment with Sun could partially
reduce the sensitivity towards Cbz. Still, it was cell line-depended and
thus, it might reect the possible heterogeneity between patients. Overall,
our study provides an understanding of cellular signaling of therapy
sequencing using Cbz in mRCC.
Disclosure Statement: e authors declare no conict of interest.
204
Status and further development of outpatient specialist
medical care in the area of urological tumors“ (ASV-WE)
Marianne Leitsmann1; Carina Stammann1; Tobias Herrmann1;
Gerald Wilms1; Björn Broge1; Roland Zielke2; Kerstin Bode-Greuel3;
Katja Krug4; Amanda Breckner4; Michel Wensing4; Markus Leibner5;
Clemens Krause5; Hannah Zwiener5; Stefanie Fähndrich5;
Lothar Weißbach6
1aQua - Institut für angewandte Qualitätsförderung und Forschung im
Gesundheitswesen GmbH , Göttingen, Deutschland
2Berufsverband der Deutschen Urologen e.V. (BvDU), Berlin, Deutschland
3Deutsches Institut für Fachärztliche Versorgungsforschung GmbH, Berlin,
Deutschland
4Abteilung für Allgemeinmedizin und Versorgunsgforschung, Medizinische
Fakultät Heidelberg, Heidelberg, Deutschland
5Zentralinstitut für die kassenärztliche Versorgung in der Bundesrepublik
Deutschland , Berlin, Deutschland
6Gesundheitsforschung für Männer gGmbH, Berlin, Deutschland
Background: Outpatient specialist medical care (ASV) aims to provide
better care for patients with complex diseases through cross-sectoral net-
working and interdisciplinarity care. e study examines the underlying
care processes in the ASV area of urological tumors, focusing on patients
with advanced or metastatic prostate cancer (PCa). We aim to explore
how far the existing ASV meets its expectations regarding innovative,
highly qualied, and sector-connecting care.
Methods: An exploratory and comparative analysis (ASV-care vs. usual
care) is carried out at the level of the structure, process and result qual-
ity met. e methodology follows a “mixed methods” approach. Work
package (WP) 1 comprises the questioning of approx. 1.800 patients. In
WP 2, ASV and non-ASV doctors are surveyed. WP 3 examines cases
of ASV vs. non-ASV patients based on anonymized case data. In WP 4,
interviews and small group discussions are held with ASV doctors, stake-
holder, patient and family representatives. e total results are processed
in workshops and recommendations for action are developed (WP 5). e
project duration is 48 months.
Result: We compiled a suitable patient questionnaire addressing e.g.,
quality of life and coordination of care. As well as a survey tool for urolo-
gists, addressing quality of patient care and intersectoral cooperation. We
further established a framework of criteria to lter for optimal patient care
based on current guidelines and a population-based registry.
Discussion: We will consider whether the results for patients with urolog-
ical tumors, specically advanced or metastatic PCa, can be transferred to
other ASV areas, and at which points the ASV should be further devel-
oped to achieve the specied goals and exploit the potential of optimized
patient care.
Conclusion: Explicit recommendations for action have to be made based
on the knowledge gained for the benet of the patients.
Disclosure Statement: e authors declare no conict of interest. e project is
funded by the Innovation Committee at the Federal Joint Committee under the
funding number 01VSF20026.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts102
222
Real-world study of cabozantinib in patients with advanced
renal cell carcinoma (aRCC) after VEGF-targeted therapy
(CASSIOPE): interim data for patients who had received
prior nivolumab
Paul Hamberg1; Pierre Bigot2; Cristina Suárez3; Philippe Barthelemy4;
Jean-Christophe Eymard5; Cristina Masini6; Pablo Gajate7;
Pascale Dutailly8; Valerie Perrot8; Giuseppe Procopio9
1Franciscus Gasthuis & Vlietland, Rotterdam, Niederlande
2Centre Hospitalier Universitaire dAngers, Angers, Frankreich
3Hospital Universitari Vall d´Hebron, and Vall d´Hebron Barcelona Hospital
Campus, Vall d´Hebron Institute of Oncology (VHIO), Medical Oncology, Spanien
4Institut de Cancérologie Strasbourg Europe, Strasbourg, Frankreich
5Institut Jean Godinot, Reims, Frankreich
6AUSL-IRCCS di Reggio Emilia, Oncology Unit, Italien
7Hospital Universitario Ramón y Cajal, Madrid, Spanien
8Ipsen, Boulogne-Billancourt, Frankreich
9Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italien
Background: Cabozantinib is a tyrosine kinase inhibitor (TKI) approved
in Europe as monotherapy for aRCC following prior VEGF-targeted
therapy, or for treatment naïve patients with intermediate/poor risk.
We report interim real-world data (RWD) on the use of cabozantinib in
patients with aRCC who have received prior VEGF-targeted therapy and
the checkpoint inhibitor (CPI) nivolumab.1
Methods: CASSIOPE (NCT03419572) is an ongoing, non-interventional
study of cabozantinib in patients with aRCC who have received prior
VEGF-targeted therapy; a pre-planned interim analysis was conducted
when 50% of patients had completed ≥ 3 months of follow-up. is post-
hoc analysis assessed patient characteristics, best overall response (BOR)
based on RECIST 1.1, dose modications and tolerability at 3months in
patients who had also received prior nivolumab.
Result: Of 337 patients included in CASSIOPE, 154 (45.7%) had received
prior nivolumab (median age, 67.5 yrs; 70.8% male, 87.7% clear-cell his-
tology, 96.1% metastatic disease; 80.8% ECOG PS 0–1). Of these patients,
58.4% initiated cabozantinib at 60mg/day; median daily dose during the
study was 40 mg. Overall, 78.6% of patients had dose modications, 66.9%
due to adverse events (AEs) (reduction 46.8% (any) and 43.5% (due to
AEs); interruption, 54.5% and 46.8%; discontinuation, 26.0% and 14.3%).
AEs were reported in 94.8% of patients, most commonly diarrhea (36.4%)
and PPE syndrome (25.3%). During the rst 3months, 58 patients had
an evaluable BOR: 39.7% had partial response, 44.8% stable disease and
12.1% progressive disease (3.4% not evaluable). ere were 17 all-cause
deaths (11.0%).
Discussion: Our ndings are consistent with interim results for the full
CASSIOPE population and contribute valuable RWD on the use of TKIs
aer prior CPI therapy.
Conclusion: is post-hoc analysis of interim CASSIOPE data suggests
that cabozantinib, used in routine care, is broadly tolerable and may
oer tumor response in patients previously treated with VEGF-targeted
therapy and nivolumab.
1Previously presented at ESMO 2021
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
253
Immune-related adverse events can predict progression-free
and overall survival in patients with metastatic renal cell
carcinoma treated with immune checkpoint inhibitors
Matteo Silberg1,2; Laura-Maria Krabbe1; Martin Bögemann1;
Andres Jan Schrader1; Katrin Schlack1
1Universitätsklinikum Münster, Klinik für Urologie und Kinderurologie, Münster,
Deutschland
2Marien Hospital Herne, Universitätsklinikum der Ruhr-Universität Bochum,
Klinik für Urologie, Herne, Deutschland
Background: Dierent combination therapies with anti-PD-1/PD-L1- or
-CTLA4 immune checkpoint inhibition (ICI) are widely used in patients
(pts) with metastatic renal cell carcinoma (mRCC). Biomarkers or clinical
characteristics predicting response to treatment are rare.
Methods: In our retrospective cohort study, we analyzed data based on
digital charts of 134 pts with mRCC receiving ICI (Nivolumab, Ipilimumab
and Nivolumab, Pembrolizumab and Axitinib or Avelumab and Axitinib)
between 2015 and 2020 at the Department of Urology, University Hospital
Muenster. To identify predictors of overall- (OS) and progression-free
survival (PFS), with a special focus on the presence of immune-related
adverse events (irAE), we used Cox regression and Kaplan-Meier-analysis.
Result: Median age was 66 years (IQR 28-85). We observed irAE in 85 pts
(63.4%). Cutaneous events were most common (38.8%) followed by endo-
crine (24.6%) and hepatic (14.2%) irAE. 49 pts (36.6%) required cortico-
steroid therapy due to irAE. In multivariate analysis the presence of irAE
(HR 0.46, P=0.008) was associated with prolonged PFS. Platelets increase
under ICI (HR 2.29, P=0.018) and lymph node metastasis (HR 1.98,
P=0.037) were associated with worse PFS. Considering OS, occurrence of
irAE (HR 0.28, P=0.002), ECOG status (HR 2.13, P=0.048), IMDC score
(HR 2.74, P=0.018) and LDH (HR 4.65, P<0.001) remained independent
predictors. In Kaplan-Meier-analysis the median PFS was signicantly
improved for the irAE subgroup (15 months) compared to in the non-
irAE subgroup (5 months, P<0.001). Median OS was not reached in the
irAE subgroup. Nevertheless, there was a signicant improvement for pts
with irAE compared to the non-irAE subgroup (25 months, P=0.002).
Corticosteroid therapy did not aect survival outcome.
Discussion & Conclusion: e presence of irAE under therapy with ICI
in pts with mRCC is associated with better PFS and OS. erefore, irAE
should be treated consequently and a permanent discontinuation of ICI
should not be decided prematurely.
Disclosure Statement: No conict of interest.
266
Interim data of eectiveness and safety of nivolumab plus
ipilimumab combination therapy (NIVO+IPI) in rst line (1L)
advanced/metastatic renal cell carcinoma (aRCC) from the
German non-interventional study (NIS) NORA
Jens Bedke1; Harald Müller-Huesmann2; Hanjo Belz3; Eyck von der Heyde4;
Martin Bögemann5; Arne Strauß6; Philipp Ivanyi7; Jörg Wiegand8;
Andrea Autengruber9; Marc-Oliver Grimm10; Viktor Grünwald11
1Universitätsklinikum Tübingen, Tübingen, Deutschland
2Brüderkrankenhaus St. Josef, Paderborn, Deutschland
3Zeisigwaldkliniken Bethanien Chemnitz, Chemnitz, Deutschland
4Onkologische Praxis am Raschplatz, Hannover, Deutschland
5Universitätsklinikum Münster, Münster, Deutschland
6Universitätsmedizin Göttingen, Georg-August-Universität Göttingen,
Göttingen, Deutschland
7Medizinische Hochschule Hannover, Hannover, Deutschland
8Gemeinschaftspraxis für Hämatologie & Onkologie am St. Josef Krankenhaus,
Moers, Deutschland
9Bristol Myers Squibb, München, Deutschland
10Universitätsklinikum Jena, Jena, Deutschland
11Universitätsklinikum Essen, Westdeutsches Tumorzentrum Essen, Essen,
Deutschland
Background: e CheckMate 214 phase 3 trial demonstrated a sustained
survival benet in 1L patients (pts) with intermediate/poor-risk aRCC for
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 103
NIVO+IPI versus sunitinib. Here, we report real-world data on eective-
ness and safety for 1L NIVO+IPI as an interim analysis of the German NIS
NORA (NCT02940639).
Methods: Adults with aRCC and 1L NIVO+IPI treatment (tx) according
to the label were eligible. e primary study objective is overall survival
(OS) over a 5-yr follow-up period. is interim analysis (database cut
Jan 31 2022) reported data on demographics, disease characteristics and
safety using descriptive statistics. Kaplan-Meier methodology was used
to estimate progression free survival (PFS, investigator assessed or per
RECIST) and OS.
Result: A total of 258 pts (78.7 % with clear cell RCC) were enrolled from
Jan 2019 - Dec 2021. Most patients (71.7%) were male and mean age was
65.8 yrs (age groups: < 65 yrs, 46.1%; ≥ 65 to < 75 yrs, 31.0%; ≥ 75 yrs,
22.9%). According to International Metastatic RCC Database Consortium
(IMDC) score, 69% had intermediate, and 26% had poor risk RCC with
proportional distribution among age groups; pts with Karnofsky score < 80
was 17.1% and a higher fraction of pts with Karnofsky score < 80 (34.1%)
was detected in elderly (≥ 75 yrs). 62.8 % of pts had prior nephrectomy.
Median follow-up was 6.3 mo, and median duration of treatment was 6.3
mo; 105 pts were still on tx, while 153 pts discontinued tx. Median PFS
was 6.6 mo (95% CI, 4.9-9.1 mo) and OS probability at 12 months was
66.1%. At least one treatment-related AE (trAE)/serious trAE of any grade
was reported in 55.8%/18.6% of pts.
Discussion & Conclusion: ese rst results on 1L NIVO+IPI in routine
care with a limited median follow-up period provides supporting infor-
mation on eectiveness and safety of NIVO+IPI in aRCC. Our real-world
patient cohort diered regarding pts characteristics when compared to
CheckMate 214, and no new safety signals were detected.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
300
Surgical management of localised renal cell carcinoma in
Hessian hospitals - a population-based analysis
Katharina Bernhardt1; Petra Neuser1; Soo-Zin Kim-Wanner1
1Hessisches Krebsregister, Hessisches Landesprüfungs- und Untersuchungsamt
im Gesundheitswesen, Landesauswertungsstelle, Frankfurt, Deutschland
Background: During the past decade, the treatment paradigm for localised
renal cell carcinomas (RCC) has shied towards nephron-sparing surgery
as oncologic outcomes have shown to be equivalent to radical nephrec-
tomy and towards minimally invasive surgery with reduced intraoperative
blood loss and shorter convalescence. To date, little data are available on
the implementation of laparoscopy in partial and radical nephrectomy in
Germany. e purpose of this study was to analyse the surgical manage-
ment of localised RCC and compare the rates of organ-saving and mini-
mally invasive resections among dierent care providers.
Methods: Data of patients with RCC diagnosed between 2015-2019 were
extracted from the database of the Hessian cancer registry. 2014 patients
with age ≥ 18 years and ICD-10 C64 were included in the analysis.
Result: 1320 of 2014 RCC were reported by 24 care providers with a UICC
stage I: 58% and II: 8%. 87% received surgical treatment. e 30-day mor-
tality aer resection was 2% and T1-2 tumours were completely excised
(R0) in 93% of the patients. Nephron-sparing surgery was observed in
67% of pT1 cases, but varied among hospitals (range: 44-79%) with a
higher rate of 72% in two high volume centres with ≥ 50 resections annu-
ally. T1 tumours were excised minimally invasive in 14% of the cases
(high volume centres: 14% and 36%) and 50% of the medical institutions
exclusively performed open surgical resections in localised RCC. Among
laparoscopically removed T1 tumours, 56% were partially and 44% were
radically resected.
Discussion: So far, comprehensive implementation of nephron-spar-
ing resections and especially minimally invasive surgery have not been
achieved. High disparities among Hessian hospitals were detected.
Nevertheless, the low 30-day mortality and high R0 rate indicated an over-
all high quality of surgical excisions.
Conclusion: More eorts have to be made for a widespread and con-
sistent implementation of the recommended therapy for localised RCC
to improve the quality of surgical treatment and reduce morbidities in
patients.
Disclosure Statement: e authors declare no conict of interest.
308
Analysis of the CLEAR study in patients (pts) with advanced
renal cell carcinoma (RCC): depth of response and ecacy for
selected subgroups in the lenvatinib (L) + pembrolizumab (P)
and sunitinib (S) treatment arms
Viktor Grünwald1; Thomas Powles2; Evgeny Kopyltsov3; Vadim Kozlov4;
Teresa Alonso Gordoa5; Masatoshi Eto6; Thomas Hutson7; Robert Motzer8;
Eric Winquist9; Pablo Maroto10; Bhumsuk Keam11; Giuseppe Procopio12;
Shirley Wong13; Bohuslav Melichar14; Frederic Rolland15; Mototsugu Oya16;
Karla Rodriguez-Lopez17; Kenichi Saito18; Alan Smith19; Camillo Porta20
1University Hospital Essen, Essen, Deutschland
2The Royal Free NHS Trust, London, England, Vereinigtes Königreich
3State Institution of HealthcareRegional Clinical Oncology Dispensary”, Omsk,
Russische Föderation
4State Budgetary Health Care InstitutionNovosibirsk Regional Clinical Oncology
Dispensary”, Novosibirsk, Russische Föderation
5Hospital Universitario Ramón y Cajal, Madrid, Spanien
6Kyushu University, Fukuoka, Japan
7Texas Oncology, Dallas, TX, USA
8Memorial Sloan Kettering Cancer Center, New York, NY, USA
9Western University, London, Ontario, Kanada
10Hospital de la Santa Creu i Sant Pau, Barcelona, Spanien
11Seoul National University Hospital, Seoul, Republik Korea
12Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italien
13Western Health, VIC, Australien
14Palacký University Medical School and Teaching Hospital, Olomouc,
Tschechische Republik
15Centre René Gauducheau Centre de Lutte Contre Le Cancer Nantes, Saint-
Herblain, Frankreich
16Keio University School of Medicine, Tokyo, Japan
17Merck & Co., Inc., Kenilworth, NJ, USA
18Eisai Inc., Woodcli Lake, NJ, USA
19Eisai Ltd., Hateld, England, Vereinigtes Königreich
20San Matteo University Hospital Foundation, Pavia, Italien
Background: In the phase 3 CLEAR study, L+P had signicant PFS and
OS benets, and improved ORR vs S in 1L advanced RCC.
Methods: Pts were randomized 1:1:1 to 1 of 3 treatment arms: L 20 mg
PO QD + P 200 mg IV Q3W; L 18 mg + everolimus 5 mg PO QD; or S
50 mg PO QD (4 wks on/2 wks o). We report PFS, OS, and ORR based
on IMDC risk group (favorable and intermediate/poor) and target kidney
lesion presence at baseline (post hoc analysis). Post hoc 6-mo landmark
analyses assessed the association between tumor shrinkage and OS. Pts
who were alive at 6 mos were grouped based on maximum tumor shrink-
age from baseline or conrmed complete response (CR) up to 6 mos.
Tumor assessments were performed by independent review committee
per RECIST v1.1.
Result: Among 1069 pts, 355 were assigned to L+P and 357 to S. Median
follow-up was 27 mos for L+P and 26 mos for S. L+P was favored vs S in
the IMDC-intermediate/poor subgroup (n=243 vs 229) for PFS (median
22.1 vs 5.9 mos, HR 0.36, 95% CI 0.28-0.47), OS (HR 0.58, 95% CI 0.42-
0.80), and ORR (72.4% vs 28.8%, odds ratio [OR] 6.60, 95% CI 4.39-
9.90) as well as in the IMDC-favorable subgroup (n=110 vs 124) for PFS
(median 28.1 vs 12.9 mos, HR 0.41, 95% CI 0.28-0.62) and ORR (68.2%
vs 50.8%, OR 2.00, 95% CI 1.17-3.42), with too few OS events to evaluate.
In pts with target kidney lesions, median PFS (22.1 vs 7.5 mos, HR 0.40,
95% CI 0.25-0.65), median OS (not reached vs 30.7 mos, HR 0.44, 95% CI
0.26-0.77), and ORR (71.8% vs 27.0%, OR 10.55, 95% CI 4.54-24.52) were
improved with L+P vs S (n=78 vs 74). In the 6-mo landmark analysis in
the L+P arm, 24 mo OS rate was 100% (95% CI not estimable [NE]-NE)
for pts with conrmed CR, and 91.7% (95% CI 53.9-98.8) both for pts
with >75% to <100%, and 100% target-lesion reduction.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts104
Discussion: In pts with target kidney lesions and across evaluable IMDC
subgroups, L+P conferred survival benets vs S similar to benets
observed in the overall population.
Conclusion: L+P improved PFS, OS, and ORR vs S in pts with target kid-
ney lesions and across evaluable IMDC risk groups. Overall, pts treated
with L+P who had >75% reduction in target lesions had similar OS rates
to pts with CR.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
326
Ecacy and safety of darolutamide in patients with
nonmetastatic castration-resistant prostate cancer (nmCRPC)
and a prostate-specic antigen doubling time (PSADT) > and
≤ 6 months
Martin Schostak1; Martin Bögemann2; Matthew R. Smith3; Neal D. Shore4;
Teuvo L.J. Tammela5; Albertas Ulys6; Egils Vjaters7; Sergey Polyakov8;
Mindaugas Jievaltas9; Murilo Luz10; Boris Alekseev11; Iris Kuss12;
Marie-Aude Le Berre13; Amir Snapir14; Toni Sarapohja14; Karim Fizazi15
1Department of Urology, Magdeburg University Medical Center, Magdeburg,
Deutschland
2Department of Urology, Münster University Medical Center, Münster,
Deutschland
3Massachusetts General Hospital Cancer Center and Harvard Medical School,
Urologic Oncology, Boston, MA, USA
4Carolina Urologic Research Center , Atlantic Urology Clinics, Myrtle Beach,
SC,USA
5Tampere University Hospital, Tampere, USA
6Institute of Oncology, Vilnius University, Vilnius, Lithuania
7Pauls Stradins Clinical University Hospital, Department Of Urology, Riga, Latvia
8N.N. Alexandrov National Cancer Centre, Department of Urology, Minsk, Belarus
9Lithuanian University of Health Sciences, Medical Academy, Department of
Urology, Kaunas, Lithuania
10Hospital Erasto Gaertner, Curitiba, Brasilien
11Hertzen Moscow Oncology Research Institute, Moscow, Russische Föderation
12Bayer AG, Berlin, Deutschland
13Bayer Healthcare, Loos, Frankreich
14Orion Corporation Orion Pharma, Espoo, Finnland
15Institut Gustave Roussy, University of Paris-Sud, Villejuif, Frankreich
Background: In the phase 3 ARAMIS trial, darolutamide (DARO) signi-
cantly improved metastasis-free survival (MFS) and Overall survival (OS)
in patients with nmCRPC and PSADT ≤10 months. Patients in ARAMIS
were stratied by PSADT ≤6 months and >6 months. Here we present
the ecacy and safety of DARO in ARAMIS participants in subgroups
by PSADT.
Methods: e double-blind, placebo-controlled phase III ARAMIS trial
randomized 1509 patients in a 2:1 ratio to receive DARO 600 mg BID
(n=955) or placebo (PBO; n=554), while continuing androgen depri-
vation therapy. Patients were stratied by PSADT (≤6 or >6 months) to
assess the eect on ecacy and safety.
Result: In the overall population, median (range) baseline PSADT was
4.4 (0.7–11.0) months in the DARO arm and 4.7 (0.7–13.0) months in the
PBO arm. Around 30% of patients in each arm had PSADT >6 months.
In the subgroup of patients with PSADT >6 months, the risk of metastasis
or death was reduced by 62% with DARO as compared with PBO (hazard
ratio [HR] 0.38; 95% condence interval [CI] 0.26–0.55), in line with both
the overall population (HR 0.41; 95% CI 0.34–0.50) and with patients
with PSADT ≤6 months (HR 0.41; 95% CI 0.33–0.52). Median (95% CI)
MFS was not estimable (40.5 months–not estimable) and 34.3 months
(30.8 months–not estimable) for patients with PSADT >6 months and
≤6 months, respectively. At nal analysis, Overall survival was improved
in both subgroups in line with overall population. e safety prole of
DARO, including AEs of interest, for patients with PSADT >6 months was
consistent with that of the overall study population.
Conclusion: e MFS benet and safety of DARO is similar in the sub-
set of patients with PSADT >6 months and the overall ARAMIS study
population
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
327
Time Course Prole of Adverse Events of Interest and Serious
Adverse Events With Darolutamide in the ARAMIS Trial
Markus Grabbert1; Christian Gratzke1; Karim Fizazi2; Neal Shore3;
Matthew Smith4; Susan Feyerabend5; Joan Carles6; Thierry Lebret7;
Egils Vjaters8; Patrick Werbrouck9; Marina Miskic10; Anja Schmall11;
Marie Aude Le Berre12; Gustavo Borghesi13; Frank Verholen14
1University Hospital Freiburg, Freiburg, Deutschland
2Institut Gustave Roussy, University of Paris Saclay, Villejuif, Frankreich
3Carolina Urologic Research Center, Myrtle Beach, SC, USA
4Massachusetts General Hospital, Boston, MA, USA
5Studienpraxis Urologie, Nuertingen, Deutschland
6Vall dHebron Institute of Oncology, Hospital Universitari Vall dHebron,
Barcelona, Spanien
7Hopital Foch, Suresnes, Frankreich
8P. Stradins Clinical University Hospital, Riga, Latvia
9AZ Groeninge, Kortrijk, Belgien
10Bayer Consumer Care AG, Basel, Schweiz
11Bayer Vital GmbH, Leverkusen, Deutschland
12Bayer Healthcare SAS, Loos, Frankreich
13Bayer AG, Berlin, Deutschland
14Bayer Healthcare SAS, Basel, Schweiz
Background: Men with nonmetastatic castration-resistant prostate cancer
(nmCRPC) are generally asymptomatic and may receive prolonged treat-
ment with androgen receptor inhibitors. Understanding the burden and
time course of adverse events (AEs) commonly associated with ARIs that
may impact patients’ daily life will help inform optimal treatment selec-
tion. We present analyses of time to AEs of interest (fatigue, falls, fracture,
hypertension, mental impairment, rash) and the cumulative incidence of
these AEs, grade 3/4 AEs, and serious AEs from the ARAMIS trial.
Methods: Men with nmCRPC were randomized 2:1 to darolutamide
(DARO; n=955) or placebo (PBO; n=554) while continuing androgen
deprivation therapy. e cumulative incidence of AEs was analyzed using
Kaplan-Meier estimates for the rst 24 months (mo) of the double-blind
(DB) period to ensure >10% of the population in each treatment cohort.
Time interval–specic analysis determined new event rates at each sched-
uled study visit.
Result: e overall incidence of AEs of interest in the DARO group was
low and ≤2% dierent from that in the PBO group, except for fatigue.
During the rst month of DARO and PBO treatment, new event rates
were very low and similar for falls (0.2%, 0.7%), fractures (0.4%, 0.5%),
mental impairment (0%, 0.4%), hypertension (1.7%, 1.1%), and rash
(0.7%, 0.2%). In men who had fatigue during the rst 24 mo (12.6%,
8.3%), almost half of the men experienced fatigue onset during the rst
month in both arms (5.9%, 4.0%). e cumulative incidence of rash was
2.9% (PBO 1.1%) at 24 mo, with half of the events occurring in the rst 4
mo and almost all being grade 1 or 2. e rate of initial onset and cumu-
lative incidence of grade 3/4 AEs and serious AEs were similar for DARO
and PBO groups over 24 months.
Conclusion: e time course prole of most AEs of interest, grade 3/4
AEs, and serious AEs conrms the safety prole of DARO, showing a sim-
ilar onset and cumulative incidence versus PBO. Most events of fatigue
were reported early in treatment, and the incidence of rash was very low,
with almost all being grade 1 or 2 events.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 105
328
Clinical benet and safety prole of darolutamide in
patients who crossed over to darolutamide from placebo
during the open-label period of the phase 3 ARAMIS study
Tilman Todenhöfer1; Susan Feyerabend1; Neal Shore2; Matthew Smith3;
Evgeny Kopyltsov4; Igor Antonyan5; Jan-Erik Damber6;
Donatello Gasparro7; Asif Yildirim8; Egils Vjaters9; Jorge Ortiz10;
Shankar Srinivasan10; Toni Sarapohja11; Karim Fizazi12
1Studienpraxis Urologie, Nuertingen, Deutschland
2Carolina Urologic Research Center, Myrtle Beach, SC, USA
3Massachusetts General Hospital, Boston, MA, USA
4BHI of Omsk Region Clinical Oncological Dispensary, Omsk, Russische
Föderation
5Kharkiv Medical Academy of Postgraduate Education, Kharkiv, Ukraine
6University of Gothenburg, Gothenburg, Schweden
7Azienda Ospedaliero-Universitaria di Parma, Parma, Italien
8Istanbul Medeniyet University Goztepe Training And Research Hospital,
Istanbul, Türkei
9P. Stradins Clinical University Hospital, Riga, Latvia
10Bayer Healthcare, Whippany, NJ, USA
11Orion Corporation Orion Pharma, Espoo, Finnland
12Institut Gustave Roussy, University of Paris Saclay, Villejuif, Frankreich
Background: Darolutamide (DARO) signicantly prolonged metasta-
sis-free survival (MFS) and overall survival (OS) vs placebo (PBO) in
men with nonmetastatic castration-resistant prostate cancer in ARAMIS.
DARO has a favorable safety prole, showing ≤2% dierence between
DARO and PBO for most adverse events (AEs) of interest associated with
androgen receptor inhibitors. Fatigue was the only AE with >10% inci-
dence in the DARO arm (13.2% vs 8.3% in PBO arm). Aer unblinding of
ARAMIS,170 patients (pts) receiving PBO crossed over (CO) to open-la-
bel (OL) DARO. Here, we present clinical benet and safety in CO pts.
Methods: Pts with nmCRPC and prostate-specic antigen (PSA) dou-
bling time ≤10 months were randomized 2:1 to DARO (n=955) or PBO
(n=554) while continuing androgen deprivation therapy. For PBO to
DARO CO pts at nal analysis, PSA outcomes were used to assess clinical
benet because the treatment duration was not long enough to assess MFS
or OS. e last outcome measurement before CO from PBO to DARO was
the CO baseline value. AEs during the double-blind (DB) and OL periods
were compared with the CO period for the same observation time, consis-
tent with the median treatment duration in CO pts.
Result: PBO to DARO CO pts had higher median PSA values (19.80 vs
7.06 ng/mL) and poorer Eastern Cooperative Oncology Group perfor-
mance status (ECOG ≥1 in 31% vs 25%) at the start of DARO treatment
compared with study entry. Median treatment duration for CO pts was 11
months. At any time aer CO, 85% of CO pts had a PSA50 response. At
16 weeks aer CO, 51% had PSA90 response. Compared with the DARO
DB period during 11 months of treatment, DARO CO pts had similar or
lower rates of any AEs (75.8% vs 70.0%), serious AEs (14.8% vs 15.3%),
and AEs leading to study drug discontinuation (5.9% vs 4.7%). Most AEs
of interest had a lower incidence in CO pts compared with the DB period.
Conclusion: Although the OS and MFS results substantiate the clear
benet of early treatment with DARO, there were consistent safety and
potential clinical benets for pts who received DARO following CO from
PBO in ARAMIS.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
390
Trends in rst-line treatment of early stage prostate cancer
with data from the Cancer Registry of Baden-Württemberg
(Germany)
Tilo Vogel1; Irina Surovtsova1; Franziska Kanz1; Bettina Balzer1;
Philipp Morakis1
1Klinische Landesregisterstelle, Krebsregister Baden-Württemberg, Stuttgart,
Deutschland
Introduction: Treatment options for early stage prostate cancer include
radical and ablative surgery, denitive radiotherapy and active sur-
veillance/ wait and see. Further, Androgen-deprivation may be used as
palliative systemic therapy. Management is guided by life expectance,
comorbidities, risk and patients preferences. e present population
based study uses data from the Cancer Registry of Baden-Württemberg
(BW) to examine trends in the management of early stage disease.
Objective: Aim of this study was to show trends in the primary treatment
modality of early stage incidence prostate cancer.
Patients and Methods: Patients with incident prostate adenocarcinoma
diagnosed between 2013 until 2019 and reported to the Cancer Registry
were included. Primary therapy modalities (surgery, radiotherapy, wait
and see/ active surveillance and systemic therapy) of early stage T1/T2
disease were analysed. Radical and ablative surgery procedures were iden-
tied based on the operation and procedure code reported to the Registry.
e frequency of each treatment modality for each year was calculated for
low, intermediate and high risk groups according to the D´Amico classi-
cation for a total number of about 10.000 patients.
Results: In this analysis, radical surgery was the most frequently applied
primary therapy (> 60%) for early stage prostate adenocarcinoma for all
risk groups. For the intermediate risk group, a slight increase in the use of
radical surgery was observed from 2013 to 2019, while systemic therapy
was less used over the years. e use of radiotherapy, the second mostly
used primary treatment, and conservative management (wait and see /
active surveillance) did not change substantially.Ablative procedures were
used with low rate and predominantly applied in the low risk group.
Conclusion: Despite radical surgery procedures for prostate cancer poses
severe side eects, data of the Cancer Registry showed their preferential
use in early stage prostate cancer for all risk groups during the years 2013
to 2019 and a trend to their increased use in the intermediate risk group.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts106
507
Clinical and molecular characterization of patients (pts)
with Neuroendocrine Prostate Cancer (NEPC) treated at a high
volume cancer center
Ray Maria Vittoria Stiens1; Saskia Ting2; Henning Reis3; Tibor Szarvas4;
Lukas Püllen4; Thomas Hilser1; Lara Helena Sichward2; Boris Hadaschik4;
Kurt Werner Schmid5; Hans-Ulrich Schildhaus6; Martin Schuler7;
Viktor Grünwald8; Isabel Virchow1
1Medical Faculty University Duisburg-Essen, West German Cancer Center,
Department of Medical Oncology, Essen, Deutschland
2Medical Faculty University Duisburg-Essen, West German Cancer Center,
Institute of Pathology, Essen, Deutschland
3University Hospital Frankfurt, Johann Wolfgang Goethe University, Institute of
Pathology, Deutschland
4Medical Faculty University Duisburg-Essen, West German Cancer Center,
Department of Urology, Essen, Deutschland
5Medical Faculty University Duisburg-Essen, West German Cancer Center,
Institute of Pathology, German Cancer Consortium (DKTK), Essen, Deutschland
6Medical Faculty University Duisburg-Essen, West German Cancer Center,
Institute of Pathology, German Cancer Consortium (DKTK), Essen,
7Medical Faculty University Duisburg-Essen, West German Cancer Center,
Department of Medical Oncology, German Cancer Consortium (DKTK), Essen,
Deutschland
8Medical Faculty University Duisburg-Essen, West German Cancer Center,
Department of Medical Oncology, Department of Urology, Essen, Deutschland
Background: Primary NEPC (p-NEPC) is a rare disease (<1%)
whereastreatment emergent (t-NEPC) can be found in 30% of metastatic
castration-resistant tumors. Reported overall survival (OS) is poor with
16 months (mo). Mechanisms accounting for resistance and response to
chemotherapy (CTX), androgen deprivation (ADT) or neuroendocrine
transdierentiation are still not understood. Here, we present rst clin-
icopathological data of a metastatic NEPC cohort, treated at the West
German Cancer Center Essen (WTZ).
Methods: Clinical and epidemiological data of NEPC patients diagnosed
between 1998 and 2021 were retrospectively retrieved from the institu-
tional database. Clinicopathological characteristics and overall survival
(OS) were investigated. Standard immunohistochemistry and extensive
mutational analyses using next generation sequencing (NGS) were per-
formed exploratory on 66 genes.
Result: 25 pts with NEPC were identied; 14 pts were classied as p-NEPC,
11 as t-NEPC. Median age was 66.2 years. Median PSA was 38.5 ng/ml.
As rst-line treatment 7 pts received palliative platinum- or taxane-based
CTX, 15 pts received an ADT and 3 pts were irradiated. Median OS was
18 mo. For 14 pts sucient surplus tissue samples could be retrieved and
validated. For 3 representative cases an exploratory NGS analysis was per-
formed. 1 pt showed no alteration, 1 pt showed a somatic BRCA1 Exon
10 mutation considered likely benign/of unknown signicance (VUS), 1
pt showed a pathogenic BRCA2 Exon10 mutation and simultaneously a
RNF43 Exon 9 mutation.
Discussion: BRCA1/2 mutations were found in 2 samples of p-NPEC
whereas the t-NEPC sample showed no alterations. e pt revealing a
pathogenic BRCA2 mutation and a concurrent mutation in RNF43 has an
extraordinary OS of 6.2 years and was alive at the last follow-up.
Conclusion: Outcome of this real-world NEPC patient cohort compares
favorably with published data. Our exploratory ndings support the
implementation of BRCA1/2 mutation testing in this patient population.
Disclosure Statement: e authors declare no conict of interest.
591
PSMA-PET- and mpMRI-guided focal dose escalated
radiotherapy in primary prostate cancer patients – a planned
safety analysis of a two-armed prospective phase II trial
(HypoFocal)
Simon K.B. Spohn1,2,3; Mark Gainey4; Marius Kamps5; Christian Gratzke5;
Michael MIX6; Juri Ruf6; Matthias Benndorf7; Sebastian Zschaeck8;
Pirus Ghadjar8; Dimos Baltas1,4; Anca-L. Grosu1,3; Constantinoos
Zamboglou1,2,3,9
1German Cancer Consortium (DKTK), Partner Site Freiburg, Deutschland
2Faculty of Medicine - University of Freiburg, Berta-Ottenstein-Programme,
Deutschland
3University Medical Center, Department of Radiation Oncology, Freiburg,
Deutschland
4University Medical Center, Division of Medical Physics - Department of
Radiation Oncology, Freiburg, Deutschland
5University Medical Center, Department of Urology, Freiburg, Deutschland
6University Medical Center, Department of Nuclear Medicine, Freiburg,
Deutschland
7University Medical Center, Department of Radiology, Freiburg, Deutschland
8CharitéUniversitätsmedizin Berlin, corporate member of Freie Universität
Berlin and Humboldt-Universität zu Berlin, Department of Radiation Oncology,
Berlin, Deutschland
9European University of Cyprus, German Oncology Center, Limassol, Zypern
Background: Due to superior intraprostatic tumour mass (ITM) cover-
age focal dose escalated radiotherapy (RT) to multiparametric magnet
resonance tomography- (mpMRI) and positron emission tomography
targeting prostate specic membrane antigen- (PSMA-PET) dened
boost volumes might improve treatment of primary prostate cancer (PCa)
patients. e non-randomized HypoFocal phase II trial investigates the
implementation of PSMA-PET in focal therapy planning. We present the
planned safety analysis aer 6 months of follow-up (FU).
Methods: Intermediate- and high-risk PCa patients with cN0 and cM0 in
mpMRI and PSMA-PET were included. Arm A was treated with 60 Gy in
20 fractions with boost up to 75 Gy to mpMRI- and PSMA-PET-dened
ITMs. Arm B was treated with single fraction high-dose-rate brachyther-
apy (HDR-BT) with 15 Gy to the prostate and boost up to 19 Gy to the
ITMs, followed by RT with 44 Gy in 20 fractions. We assessed gastro-
intestinal (GI) and genitourinary (GU) toxicities according to CTCAE
v5.0, IPSS score and quality of life (QoL) with EORTC questionnaires
QLQ-PR25 and QLQ-PR30.
Result: 25 patients were enrolled in each arm in two centers (Freiburg and
Berlin). Median boost volumes were 10.2 ml in arm A and 6.8 ml in arm B.
Median mean dose to the boost volume was 70 Gy in arm A and median
D90 to was 19 Gy in arm B. Cumulative grade 2 GU and GI toxicities were
36% and 16% in arm A and 48% and 12% in arm B. No grade 3 toxicity
was observed at 6 months FU. Toxicities, IPSS and QoL-scores were not
statistically signicantly dierent between baselines and 6 months of FU.
Two grade 3 GI toxicities were observed 9 and 12 FU, related to biopsy
Discussion: Combined PSMA-PET and mpMRI-based boost denition
results in signicantly larger volumes and focal dose escalation was feasi-
ble with acceptable acute toxicities without compromising QoL.
Conclusion: Implementation of PSMA-PET for focal therapy planning
should be investigated in larger cohorts. Radiation proctitis demands
careful management.
Disclosure Statement: e authors declare no conict of interest. Abstract was
submitted to EMUC2021.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 107
780
Symptomatic vs. asymptomatic renal cell carcinoma
in Germany: 39-months follow-up data from the non-
interventional, prospective VERSUS study by d-uo
Manfred Johannsen1; Rolf Harald Eichenauer2; Jörg Klier3; Frank König1;
Robert Schönfelder2; Jörg Schröder1; Elke Hempel1; Christian Doehn4
1Berlin, Berlin, Deutschland
2Hamburg, Hamburg, Deutschland
3Köln, Köln, Deutschland
4Lübeck, Lübeck, Deutschland
Background: In May 2018, the German Uro-Oncologists (Deutsche
Uro-Onkologen, d-uo) opened their prospective VERSUS study
(VERSorgUngsStudie, VERSUS) for the documentation of outpatient
diagnosis and treatment of urological tumors. is analysis addressed
the question whether age and tumor stage at diagnosis diered between
symptomatic vs. asymptomatic renal cell carcinoma (RCC) cases.
Methods: VERSUS is a nation-wide non-interventional, prospective,
multicentric study for the documentation and evaluation of outpatient
diagnosis, treatment and follow-up of urological tumors using descrip-
tive statistics. In this analysis we evaluated patients with rst diagnosis of
RCC. In the d-uo database, the cause of rst diagnosis (e.g. early detec-
tion) can be documented.
Result: Up to August 2021, 10.0799 patients with rst diagnosis of a uro-
logical tumor were documented. Out of these, 790 patients (7.8%) had
RCC. 70.5% were men and 29.5% were women, median age was 70.0 years
(men 69.9, women 70.1). In 230 cases (32.8%, median age 68.6 years),
RCC was diagnosed because of symptoms. Patients wih symptoms had
UICC stage I and IV in 49.4% and 16.3%, respectively. In contrast, asymp-
tomatic patients had UICC stage I and IV in 73.2% and 2.4%, respectively.
Discussion: Patients with symptomatic RCC are younger and display
more unfavourable tumor stages at diagnosis.
Conclusion: e VERSUS study continues to collect epidemiologic and
clinical data of patients with RCC.
Disclosure Statement: e authors declare no conict of interest.
794
Early detected vs. non-early detected prostate cancer
in Germany: 39-months follow-up data from the
non-interventional, prospective VERSUS study by d-uo
Frank König1; Rolf Harald Eichenauer2; Jörg Klier3; Manfred Johannsen1;
Robert Schönfelder2; Jörg Schröder1; Elke Hempel1; Christian Doehn4
1Berlin, Berlin, Deutschland
2Hamburg, Hamburg, Deutschland
3Köln, Köln, Deutschland
4Lübeck, Lübeck, Deutschland
Background: In May 2018, the German Uro-Oncologists (Deutsche
Uro-Onkologen, d-uo) opened their prospective VERSUS study
(VERSorgUngsStudie, VERSUS) for the documentation of outpatient
diagnosis and treatment of urological tumors. is analysis addressed the
question whether age and tumor stage at diagnosis diered between early
detected vs. non-early detected prostate cancer (PCa) cases.
Methods: VERSUS is a nation-wide non-interventional, prospective,
multicentric study for the documentation and evaluation of outpatient
diagnosis, treatment and follow-up of urological tumors using descriptive
statistics. In this analysis we evaluated patients with rst diagnosis of PCa.
In the d-uo database, the cause of rst diagnosis (e.g. early detection) can
be documented.
Result: Up to August 2021, 10.079 patients with rst diagnosis of a uro-
logical tumor were documented. Out of these, 6.291 patients (62.4%) had
PCa. In 3000 cases (47.7%), PCa was diagnosed following early detection
vs. 3.291 cases (52,3%) without early detection.
Median age of patients with early-detected vs. non-early detected PCa
was 73.3 vs. 76.7 years, respectively. TNM- -stages were available in 4.456
(70.8%) patients. Patients with early-detected PCa had stage T1 and M1 in
59.8% and 2.9% while patients with non-early detected PCa had stage T1
and M1 in 56.7% and 7%.
Discussion: Patients with early-detected PCa were younger and had
more favourable tumor stages at rst diagnosis than those with non-early
detected PCa.
Conclusion: e VERSUS study continues to collect epidemiologic and
clinical data of patients with PCa.
Disclosure Statement: e authors declare no conict of interest.
795
Symptomatic vs. asymptomatic urothelial carcinoma in Germany:
39-months follow-up data from the non-interventional;
prospective VERSUS study by d-uo
Rolf Harald Eichenauer1; Manfred Johannsen2; Jörg Klier3; Frank König2;
Robert Schönfelder1; Jörg Schröder2; Elke Hempel2; Christian Doehn4
1Hamburg, Hamburg, Deutschland
2Berlin, Berlin, Deutschland
3Köln, Köln, Deutschland
4Lübeck, Lübeck, Deutschland
Background: In May 2018, the German Uro-Oncologists (Deutsche
Uro-Onkologen, d-uo) opened their prospective VERSUS study
(VERSorgUngsStudie, VERSUS) for the documentation of outpatient
diagnosis and treatment of urological tumors. is analysis addressed
the question whether age and tumor stage at diagnosis diered between
symptomatic vs. asymptomatic urothelial carcinoma (UC) cases.
Methods: VERSUS is a nation-wide non-interventional, prospective,
multicentric study for the documentation and evaluation of outpatient
diagnosis, treatment and follow-up of urological tumors using descriptive
statistics. In this analysis we evaluated patients with rst diagnosis of UC.
In the d-uo database, the cause of rst diagnosis (e.g. early detection) can
be documented.
Result: Up to August 2021, 10.079 patients with rst diagnosis of a uro-
logical tumor were documented. Out of these, 2.533 patients (25.1%)
had UC. 77.5% were men and 22.5% were women, median age was 75.2
years (men 75.3, women 74.3). In 1.404 cases (55.4%), UC was diagnosed
because of symptoms vs. 1.129 cases (44.6%) without symptoms. Patients
with symptomatic UC had stage T1, T2 and M1 in 30.9%, 16.4% and 2.3%,
respectively. In contrast, patients with asymptomatic UC had stage T1, T2
and M1 in 26.8%, 12.4% and 0.7%, respectively.
Discussion: Patients with symptomatic UC do not dier with regard to
age from those with asymptomatic UC at diagnosis. However, percent-
age of tumor stage UICC 0 was lower and stage UICC IV was higher in
patients with symptomatic compared to those with asymptomatic UC.
Conclusion: e VERSUS study continues to collect epidemiologic and
clinical data of patients with UC.
Disclosure Statement: e authors declare no conict of interest.
880
The cellular dissociation grading system in squamous cell
carcinoma of the penis
Hayel Derani1; Oliver Hakenberg2; Andreas Erbersdobler1
1Universität Rostock, Medizinische Fakultät, Institut für Pathologie, Rostock,
Deutschland
2Universitätsklinikum Rostock: Urologische Klinik und Poliklinik, Rostock,
Deutschland Derani, Hakenberg, Erbersdobler.
Background: e lymph node status (pN) is the most important predic-
tor of survival in patients with invasive penile squamous cell carcinoma
(SCC). Criteria should be identied to improve the prediction of pN. In
this retrospective Study, the cellular dissociation grade (CDG) and WHO
grade (WHO-G) were examined as possible prognostic factors for pN.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts108
Methods: Collective: 101 cases of penile SCC (2014-2020, Rostock
University). e HPF with the highest budding activity and the smallest
nest size of tumor cells was chosen. Tumor bud is dened as a nest with
< 5 tumor cells. Tumor budding (TB) was scored as 1/2/3 according to
number of buds/HPF: 0 / <5 / ≥ 5 . Nest size (ZNG) was scored as 1/2/3/4
aer the number of tumor cells/nest: >15 / 5-15 / 2-4 / 1 . CDG was scored
as 1/2/3 according the sum of (TB+ZNG): 2-3/4-5/6-7.
Results: Comparison of relationship of both grading systems with pN:
Specicity: WHO-G = 0.641, CDG = 0.743. Sensitivity: WHO-G= 0.7 ,
CDG= 0.9 . Negative predictive value: WHO-G = 0.806, CDG= 0.935.
Positive predictive value: WHO-G= 0.5 , CDG= 0.642. P-values for two-
tailed asymptomatic signicance with Pearsons chi-square test were 0.134
between pN and WHO-G, and 0.001 between pN and CDG. P-values of
the statistical impact on pN were 0.052 for WHO-G und 0.001 for CDG
aer univariate analysis.
Discussion: e CDG had higher prognostic value for pN than the
WHO-G. e sensitivity, specicity, positive and predictive values for pN
were signicantly higher with CDG than with WHO-G. pN showed a sig-
nicant association with CDG, but no signicant association with WHO-
G. ese results are consistent with similar international studies in other
organs.
Conclusion: A grading system with features of tumor budding provides
much better prognostic information than a grading system based on cel-
lular atypia in squamous cell carcinoma of the penis.
Disclosure Statement: e authors declare no conict of interest.
881
An adjusted indirect treatment comparison (ITC) of
enzalutamide (ENZ) versus docetaxel (DOC) for metastatic
hormone-sensitive prostate cancer (mHSPC)
Carsten Ohlmann1; Andrew Armstrong2; Christian Gratzke3;
Jennifer Sugg4; Arijit Ganguli4; Eugen Dornstauder5;
Marco Groß-Langenho5; Reinhard Brauner5; Arnulf Stenzl6
1Johanniter-Krankenhaus Bonn, Bonn, Deutschland
2Duke University, Durham, USA
3Universitätsklinikum Freiburg, Freiburg im Breisgau, Deutschland
4Astellas, Northbrook, USA
5Astellas Pharma GmbH, München, Deutschland
6Eberhard Karls Universität Tübingen, Tübingen, Deutschland
Background: Randomized controlled trials (RCTs) have evaluated ENZ
or DOC vs androgen deprivation therapy (ADT) in patients with mHSPC.
However, no head-to-head RCT has directly evaluated ENZ vs DOC in
mHSPC. is Bucher-adjusted ITC complying with health technol-
ogy assessment (HTA) methods in Germany compared ENZ + ADT vs
DOC + ADT using data from four RCTs with similar study and patient
characteristics.
Methods: HTA inclusion criteria were used to identify mHSPC popula-
tions from four RCTs: the ARCHES and ENZAMET modied intent-to-
treat (mITT) and safety populations, the STAMPEDE M1 ecacy and
modied safety populations, and the CHAARTED ITT ecacy popula-
tion. An adjusted ITC compared ENZ + ADT vs DOC + ADT for over-
all survival (OS) and time to rst serious adverse event (SAE). Several
approaches to account for crossover patients in each RCT were applied.
Result: e ITC included data from 3565 patients for ecacy (OS) and
2766 for tolerability (SAEs) and found a statistically signicant advantage
for ENZ + ADT over DOC + ADT for both OS (HR [95% CI], 0.76 [0.60–
0.95]; p=0.0149) and time to rst SAE (HR [95% CI], 0.10 [0.06–0.16];
p<0.0001). ese advantages were conrmed under each crossover cor-
rection method. e OS advantage of ENZ + ADT over DOC + ADT also
remained signicant (HR [95% CI], 0.76 [0.59–1.00]; p=0.0479) if the ITC
included only data from the ARCHES and STAMPEDE RCTs (N=2153).
Discussion: In the absence of head-to-head RCTs, ITC is an accepted,
valuable method for statistically comparing outcomes from RCTs with
similar designs and patients. Limitations include dierences among RCTs
(eg, patient and disease characteristics) that cannot be fully compensated
by ITC methods and could confound cross-trial comparisons. is analy-
sis did not address outcomes from triplet therapy.
Conclusion: Our study suggests an OS benet of ENZ + ADT vs DOC
+ ADT in patients with mHSPC. RCT data are required to conrm this.
Disclosure Statement: e authors declare no conict of interest.
900
Cardiovascular comorbidities in patients with secondary
malignancies involving the genitourinary tract
Bernhard Koch1; Marcus Bauer2; Lutz Uacker1; Dirk Heimbach3
1St. Vincenz-Krankenhaus, Medizinische Klinik, Innere Medizin 1, Datteln,
Deutschland
2St. Vincenz-Krankenhaus, Medizinische Klinik, Innere Medizin 2, Datteln,
Deutschland
3St. Vincenz-Krankenhaus, Urologische Klinik, Datteln, Deutschland
Background: Cancer associated thrombosis is a potential complication
during the course of a malignant disease which may be related to the
activity of inammatory bystander cells of the tumoral microenvironment
(TME). e participation of TME cells may result in cardiovascular events
(CVE) whose risk may be increased in double maligancies. e propabil-
ity of double malignancies is raised in patients with neoplasms of the gen-
itourinary (GU) tract because prostate and urothelial cancer may occur
synchronously (1) or metachronously, and because urothelial cancer may
reoccur several times at dierent locations during patient`s histories (2).
Methods: We analysed the data bank of our hospital for reports on CVE
in patients with malignancies of the GU tract and related secondary
neoplasms.
Result: In the data set we found 265 patients with malignancies of the
GU-tract with secondary tumors either of other GU-locations or other
organs or malignancies of the hematopoetic (HP) system. In 51 % of these
cases CVE were reported during their lifetime. e correlation was most
obvious in patients with multifocal urothelial cancer. In some cases the
rst manifestations of the CVE were reported preceding the onset of the
malignancy.
Discussion: e remarkable occurence of CVE, which were reported in
patients with secondary malignancies involving the GU-Tract, indicates
the involvement of vascular related phenomena within the development
and course of a malignant process.
Conclusions: e evaluation of comorbidities of patients with secondary
malignancies may help to judge the extent of the contribution of nontu-
moral bystander cells to the course of the malignant process.
References:
1. PMID: 18774459
2. PMID: 26011327
Disclosures: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 109
945
Treatment of Patients with Muscle-Invasive and Metastatic
Bladder Cancer in Germany. Real World Data from the Quality
Assurance Initiative on behalf of the Working
Groups Urological Oncology (AUO) and Medical Oncology
(AIO) of the German Cancer Society (DKG)
Carsten Ohlmann1; Markus Kerkmann2; Laura Holtmann2;
Jürgen Gschwend3; Margitta Retz3; Maike de Wit4
1Klinik für Urologie, Johanniter Krankenhaus Bonn, Bonn,
2MMF GmbH, Münster, Deutschland
3Klinik und Poliklinik für Urologie, Universitätsklinikum rechts der Isar der
Technischen Universität München, München, Deutschland
4Klinik für Innere Medizin, Hämatologie, Onkologie und Palliativmedizin,
Vivantes Klinikum Neukölln, Berlin, Deutschland
Background: e S3-guideline on bladder cancer recommends a rad-
ical cystectomy and a cisplatin-based perioperative chemotherapy
(POC) in patients (pts) with muscle-invasive bladder cancer (MIBC).
Recommendation for metastatic urothelial carcinoma (mUC) is cispla-
tin-based or immuno-oncological (IO) treatment in platinum (Pt) ineligi-
ble pts or as 2nd line therapy. Aim of the study was to obtain representative
data on clinical routine treatment of MIBC and mUC in Germany.
Methods: A nationwide survey was performed to obtain data on stage-re-
lated patient volume in hospitals and oce-based physicians. Based on
these results, a representative sample of treatment data was collected ret-
rospectively from pts records with MIBC and mUC.
Result: Data from 956 pts (MIBC 576; mUC: 380) were collected. 49.8%
of MIBC pts received a systemic therapy, 80.4% of them received cispla-
tin/gemcitabine. 50,2% were treated with a cystectomy without POC.
Signicant factors for cystectomy without POC was higher age >75 years
(Odds ratio (OR) 4.91, 95% CI 3.01-8.11, p<0.001) and Pt ineligible pts
(OR 2.15, 95% CI 1.30-3.59; p=0.003). Treatment decision without inter-
disciplinary tumor board was also correlated with no POC (OR 2.43,
95% CI 1.65-3.61, p<0.001). In mUC Pt pretreated pts are most likely to
receive IO therapy (OR 12.07, 95% CI 6.94-21.82, p<0.001). Other sig-
nicant factors are positive PD-L1 status (OR 3.72, 95% CI 1.30-5.71,
p<0.001), higher age > 75 years (OR 2.83, 95% CI 1.43-5.73, p=0.003) and
Pt-ineligible pts (OR 2.57, 95%CI 1.30-5.71, p=0.007).
Discussion: e “gold standard” cisplatin/gemcitabine is established in
Germany if pts are treated with POC. Nonetheless half of the MIBC pts
did not receive a POC, especially if treatment-decision is not discussed in
a tumor board. In mUC IO therapy is established as 2nd line therapy aer
a Pt-based treatment.
Conclusion: Although the guideline recommendations are largely imple-
mented, there is potential for optimization, especially in the establishment
of interdisciplinary tumor boards.
Disclosure Statement: e authors declare no conict of interest.
952
Overall survival with darolutamide versus placebo in
combination with androgen-deprivation therapy and
docetaxel for metastatic hormone-sensitive prostate cancer in
the phase 3 ARASENS trial
Tilman Todenhöfer1; Matthew R. Smith2; Maha Hussain3; Fred Saad4;
Karim Fizazi5; Cora N. Sternberg6; David Crawford7; Evgeny Kopyltsov8;
Chandler H. Park9; Boris Alekseev10; Alvaro Montesa Pino11; Dingwei Ye12;
Francis Parnis13; Teuvo Tammela14; Hiroyoshi Suzuki15; Heikki Joensuu16;
Silke Thiele17; Rui LI18; Iris Kuss17; Bertrand Tombal19
1Studienpraxis Urologie, Nürtigen, Deutschland
2Massachusetts General Hospital Cancer Center, Boston, MA, USA
3Northwestern University, Feinberg School of Medicine, Chicago, IL, USA
4University of Montreal Hospital Center, Montreal, Quebec, Kanada
5Institut Gustave Roussy, University of Paris-Saclay, Villejuif, Frankreich
6Englander Institute for Precision Medicine, Weill Cornell Department of
Medicine, Meyer Cancer Center, New York-Presbyterian Hospital, New York, NY,
USA
7UC San Diego School of Medicine, San Diego, CA, USA
8Clinical Oncological Dispensary of Omsk Region, Omsk, Russische Föderation
9Norton Cancer Institute, Louisville, KY, USA
10P. Hertsen Moscow Oncology Research Institute, Moscow, Russische
Föderation
11UGC Intercentros de Oncología Médica, Hospitales Universitarios Regional y
Virgen Victoria, IBIMA, Málaga, Spanien
12Fudan University Shanghai Cancer Center, Shanghai, Xuhui District, China, VR
13Ashford Cancer Centre Research, Kurralta Park, SA, Australien
14Tampere University Hospital, Tampere, Finnland
15Toho University Sakura Medical Center, Chiba, Japan
16Orion Corporation Orion Pharma, Espoo, Finnland
17Bayer AG, Berlin, Deutschland
18Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ, USA
19Division of Urology, IREC, Cliniques Universitaires Saint Luc, UCLouvain,
Brussels, Belgien
Background: Darolutamide (DARO) is a structurally distinct androgen
receptor inhibitor that demonstrated improved overall survival (OS)
and metastasis-free survival vs placebo (PBO) in patients (pts) with
nonmetastatic castration-resistant prostate cancer (CRPC). We inves-
tigated whether DARO in combination with androgen-deprivation
therapy (ADT) + docetaxel would increase OS in pts with metastatic hor-
mone-sensitive prostate cancer (mHSPC) in the ARASENS study.
Methods: is international, double-blind, phase 3 study enrolled pts
who were randomized 1:1 to DARO 600 mg twice daily or matching PBO
in addition to ADT + docetaxel, stratied by extent of disease according
to TNM (M1a-c) and alkaline phosphatase levels. e primary endpoint
was OS. Secondary ecacy endpoints included time to CRPC, time to
pain progression, time to rst symptomatic skeletal event (SSE). Safety
was also assessed.
Result: From Nov 2016 to June 2018, 1306 pts were randomized. At the
primary data cuto (Oct 25, 2021), DARO signicantly decreased the risk
of death by 32.5% vs PBO (HR 0.675, 95% CI 0.568–0.801; P<0.0001). e
signicant OS benet was consistent across prespecied. DARO signi-
cantly delayed time to CRPC versus PBO (HR 0.357, 95% CI 0.302–0.421;
P<0.0001), Time to pain progression (HR, 0.792, 95% CI 0.660–0.950;
P=0.0058) and time to rst SSE. TEAEs were similar between treatment
arms with incidences of the most common TEAEs (≥10%) being highest
during the overlapping docetaxel treatment period, with grade 3/4 TEAEs
of 66.1% for DARO and 63.5% for PBO.
Conclusion: In pts with mHSPC, early treatment combining DARO with
ADT + docetaxel signicantly increased OS and improved key secondary
endpoints vs ADT + docetaxel alone. e incidence of TEAEs was similar
both arms.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts110
Geriatric Oncology
Poster
233
Multicentric validation of a comprehensive geriatric
assessment to predict functional outcome and mortality
following urooncological operations
Christian Fiebig1; Andreas Kahlmeyer2; Hannes Bannert1; Helge Taubert3;
Sven Wach3; Lukas Koneval4; Sebastian Graf5; Decio Maria Folchini6;
Sameh Alalem7; Karl-Günter Gaßmann8; Bernd Wullich3
1Universitätsklinikum Erlangen, Urologische und Kinderurologische Klinik,
Erlangen, Deutschland
2Urologie am Weinberg, Urologische Belegabteilung Elisabeth-Krankenhaus
Kassel, Kassel, Deutschland
3Universitätsklinikum Erlangen, Urologische und Kinderurologische Klinik,
Erlangen, Deutschland
4Universitätsklinikum Würzburg, Klinik und Poliklinik für Urologie und
Kinderurologie, Würzburg, Deutschland
5Kepler Universitätsklinikum, Klinik für Urologie und Andrologie, Linz, Österreich
6Zentralkrankenhaus Bozen, Klinik für Urologie, Bozen, Italien
7SHG-Kliniken Völklingen, Klinik für Urologie, Kinderurologie und urologische
Onkologie, Völklingen, Deutschland
8Malteser Waldkrankenhaus St. Marien, Geriatrie-Zentrum Erlangen, Erlangen,
Deutschland
Background: We present an interim analysis of a multicentric validation
of a novel comprehensive geriatric assessment. is so called ’Erlangen
Index’ (EI) aims to predict the postoperative outcome and mortality of
geriatric cancer patients regarding urooncological operations.
Methods: Prospective observation of patients ≥ 70 years undergoing elec-
tive cystectomy, prostatectomy, or kidney cancer surgery. Preoperatively,
a geriatric assessment was performed. e clinical endpoints were long-
term functional deterioration (Barthel-Index) at days 30 and 180, as well
as mortality at day 180. is assessment is currently performed in four
urological centers (Würzburg, Bozen, Linz, Völklingen) to validate the
the‘EI’.
Result: 159 patients were included in the reference cohort (Erlangen),
106 patients were included in the validation centers. Within the refer-
ence cohort, EI showed a correlation of high-risk patients (EI ≥ 4) with
a functional deterioration at day 30, day 180, and an increased mortality.
Regarding the deterioration of outcome aer 30 days (Würz.: sens=91%,
spec=42%; Linz: sens=74%, spec: 40%) and aer 180 days (Würz.:
sens=50%, spec=91%), similar results were already shown in the valida-
tion centers. In addition, a signicantly reduced survival rate of high-risk
patients can be observed in the reference cohort (χ²(1) = 16.944, p< 0.001)
as well as in the validation centers (χ²(1) = 4.594, p=0.032).
Discussion: In two validation centers (Würzburg and Linz), a preoper-
atively reliable identication of high risk patients can be achieved by the
‘EI’. Due to low numbers of patients recruited at the validation centers
(especially Bozen and Völklingen) so far, no reliable information about
mortality can be displayed.
Conclusion: is rst interim evaluation shows that the so called
‘Erlangen Index’ enables us to identify high-risk cancer patients prior to
operative interventions not only in the reference cohort (Erlangen) but
also in external centers.
Disclosure Statement: e authors declare no conict of interest.
499
Results of the Evaluation of a Complex Supportive
Intervention to Promote Physical Functioning of Older
Patients with Cancer
Eni Shehu1; Sigrid Roggendorf1; André Golla2; Gundula Hübner3;
Gabriele I. Stangl4; Andreas Lau5; Andrea Diestelhorst6; Dirk Vordermark6;
Anke Steckelberg1; Heike Schmidt1,6
1Institute of Health and Nursing Science, Medical Faculty of Martin Luther
University Halle-Wittenberg, Halle (Saale), Deutschland
2Institute of Rehabilitation Medicine, Medical Faculty of Martin Luther University
Halle-Wittenberg, Halle (Saale), Deutschland
3Institute for Psychology, Martin Luther University Halle-Wittenberg, Halle
(Saale), Deutschland
4Institute for Agricultural and Nutritional Science, Martin Luther University Halle-
Wittenberg, Halle (Saale), Deutschland
5Institute of Sport and Sport Science, Martin Luther University Halle-Wittenberg,
Halle (Saale), Deutschland
6Clinic and Outpatient Clinic for Radiotherapy, University Hospital Halle (Saale),
Halle (Saale), Deutschland
Background: In older cancer patients, physical function (PF) may decline
during and aer therapy despite tailoring oncologic therapy to individual
risk factors. erefore, strategies are needed to promote activity and pre-
vent deterioration of daily functioning, self-care and health-related qual-
ity of life (HRQOL).
e project aimed to pilot-test and evaluate a multimodal home-based
intervention to promote PF in older cancer patients during outpatient
radiotherapy, regarding feasibility, acceptance, potential benet of the
intervention and the digital (DI) versus paper-based (PI) instructions.
Methods: Participants underwent assessments of PF at baseline (T0 and
aer 12 weeks, end of the intervention (T1): TUG, 6mWT, chair rise
test, hand strength, physical activity (PA) level (PASE), nutritional status
(BIA), cognition (MMST, clock test), depression (PHQ9), social support
and HRQOL (EORTC QLQ-C30, ELD14). Based on the results and per-
sonal goals they received individual recommendations regarding PA and
nutrition aiming for independent home-based realisation. Aer 16 weeks
current PA, nutrition and HRQOL was assessed (T2).
Results: Participants (n=24, heterogeneous diagnoses, n=14 women,
mean age 70±7 years) were randomized (DI vs. PI). Between time points,
mean values of PF (EORTC QLQ-C30) showed no clinically relevant dif-
ference (>10 pts.) but large individual variance: T0: 77±16, T1: 76±20,
T2: 72±24. Patients appreciated the tailored recommendations and both
formats of instruction. ey reported motivation, social support, positive
eects of the training, activity diary, independent execution of exercises
and pedometers as facilitators. Barriers comprised mainly symptoms e.g.
fatigue, mucositis, pain and radiation side-eects.
Conclusion: e assessment-based tailoring of activity and nutritional
recommendations was appreciated. e unsupervised PA program was
feasible thus providing a possible digitally supported alternative to on-site
training for older patients with cancer especially in rural areas with di-
cult access to the clinic.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 111
788
Treatment in an elderly population ≥ 75 years (yrs.) with
pancreatic ductal adenocarcinoma (PDAC) – Real World Data
(RWD) from the PANDADETECT (PANDA) registry
Daniel Benitez Reinhardt1; Celine Lugnier1; Anna-Lena Kraeft1;
David Witte1; Jens Christmann2; Rabia Safaei1; Peter Leukers1;
Georgia Evripidou1; Thies Lindert1; Nadine Höken1; Inke Feder2;
Magdalena Keller1; Lukas Witkowski1; Monika Janot-Matuschek3;
Orlin Belyaev3; Waldemar Uhl3; Andrea Tannapfel2;
Anke Reinacher-Schick1; Stefanie Nöpel-Dünnebacke1
1Katholisches Klinikum Bochum, St. Josef Hospital Bochum, Ruhr Universität
Bochum, Mediznische Klinik V für Hämatologie und Onkologie mit
Palliativmedizin, Bochum, Deutschland
2Institut für Pathologie - Georgius Agricola Stiftung Ruhr, Institut für
Pathologie - der Ruhr-Universität Bochum am Berufsgenossenschaftlichen
Universitätsklinikum Bergmannsheil , Bochum, Deutschland
3Katholisches Klinikum Bochum, St. Josef Hospital Bochum, Ruhr Universität
Bochum, Allgemein- und Viszeralchirurgie, Bochum, Deutschland
Purpose: PDAC displays high tumor associated mortality and is rising in
incidence worldwide. With a median age of 72 years (yrs.) it mostly eects
elderly, who are still underrepresented in randomized clinical trials. RWD
could play an increasing role in health care decisions.
Material and Methods: Panda is a monocentric registry capturing clini-
cal data and biomaterial of patients (pts.) with and at risk for PDAC pre-
senting at St. Josef-Hospital, pancreatic cancer center, Ruhr-University
Bochum. We retrospectively compared three age groups (≥75 yrs. (E). vs.
70-74 yrs. (YE) vs. <70 yrs. (Y) diagnosed from 2016 to 2021 concerning
data on treatment modality including surgery and chemotherapy (ctx).
Results: 810 pts. with PDAC were analyzed. Mean age was 66,5 yrs., 428
men and 383 women, Y comprised 471, YE 140 and E 199. 146 pts. (Y/
YE/E: 74/29/43) were resected curatively intended. 347 mPDAC/LAPC
pts. received CTX (Y/YE/E; 209/63/75). Of Y 192 (85%) were recom-
mended to initial therapy with FOLFIRINOX (FFX), of YE 44 (83%)
FFX. Of E 27 (36.0%) received FFX, 29 (38.7%) varying 2-drug combina-
tions,15 (20.0%) monotherapy. Mean age of E primarily recommended to
BSC was 82,4 yrs. (27 pts.).
Discussion:: RWD from Panda comprises pts. ≥75 as 24.5% of enrolled
pts. ough being adequately represented among the pts. receiving resec-
tion, systemic treatment applied varies more than in younger pts. Still, the
majority of E recommended to ctx received combination therapy. 13.6%
of E veriably received just supportive treatment and represent a very old
and possibly frail cohort. Due to retrospective data capture a substantial
number of pts. were lost to documentation.
Conclusion:: Interdisciplinary cancer centers oer intense treatment
options including curative resection for E.
Elderly pts. represent a clinically signicant, yet very heterogenous sub-
group. Since the demand for cancer treatment for elderly patients will
increase within the next decades RWD will be an important source for
tailoring optimized treatment. Data on toxicity, dose reduction and sur-
vival will be presented.
Disclosure Statement: e authors declare no conict of interest.
921
Ecacy and tolerability of uorouracil, leucovorin, oxaliplatin
and docetaxel (ot) in real world patients with advanced
gastric and gastroesophageal cancer: does age really matter?
christian Möhring1, Aliki Timotheou1, Adrianna Mańczak1, Farsaneh Sadeghlar1,
Taotao Zhou1, Robert Mahn1, Alexandra Bartels1, Malte Monin2, Marieta Toma3,
Georg Feldmann2, Peter Brossart2, Mümtaz Köksal4, Gustavo R. Sarria4, Frank A.
Giordano4, Philipp Lingohr5, Azin Jafari5, Jörg C. Kal5, Christian P. Strassburg1,
Maria Angeles Gonzalez-Carmona1
1Universitätsklinik Bonn, Medizinische Klinik und Poliklinik I, Bonn, Deutschland
2Universitätsklinik Bonn, Medizinische Klinik und Poliklinik III, Bonn, Deutschland
3Universitätsklinik Bonn, Institut für Pathologie, Bonn, Deutschland
4Universitätsklinik Bonn, Klinik für Strahlentherapie und Radioonkologie, Bonn,
Deutschland
5Universitätsklinik Bonn, Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax-
und Gefäßchirurgie, Bonn, Deutschland
Background: Fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT)
regimen has shown strong ecacy as perioperative therapy for patients
with locally advanced gastric (GC) and gastroesophageal (AEG) carci-
noma. In the palliative situation, FLOT is recommended only for young
t patients. Data of ecacy and tolerability of FLOT in elderly patients
are scarce and controversial. us, this study aimed to provide real-life
experience of elderly patients with GC and AEG treated with FLOT as rst
line palliative chemotherapy.
Methods: Patients with advanced or metastatic GC or AEG and treated
with FLOT as rst line palliative therapy between 2010 and 2021 were
analyzed. Patients were grouped into <65-years old (n=35) and ≥65-years
old (n=22) groups. Overall survival (OS), progression free survival (PFS),
feasibility and toxicity were analyzed.
Result: e median OS was 10.4 months with no signicant dierence
between both groups (HR 0.86; 95% CI: 0.48, 1.57; p=0.632). e ECOG
performance status showed powerful inuence on OS in the subgroup
analysis with median OS of 12.3 months for ECOG=0 compared to 5.0
months for ECOG≥1 (p=0.015) as well as in multivariate analysis (HR:
2.62; 95% CI: 1.36, 5.04; p=0.004).
Discussion: e present study suggests a survival benet of the FLOT
regimen as rst-line therapy in a real-life cohort with advanced and met-
astatic GC and AEG. e ECOG performance status showed a stronger
prognostic value than patient age.
Conclusion: In palliative situation FLOT displays an ecient treatment
option for patients with a good ECOG performance status and should
therefore be considered in the therapeutic decision making of elderly
patients with GC and AEG.
Disclosure Statement: Author MG has contributed to advisory boards for Roche,
Eisai, BMS, MSD and AZ. However, these activities have no potential conicts of
interest with the manuscript. None of the other authors have any potential conicts
(nancial, professional or personal) that are relevant to the abstract.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts112
Gynecologic Cancer
Best-of-Abstract-Vortrag
588
The histone H2B monoubiquitination supports aggressive
properties of cervical but not endometrium carcinoma
Florian Wegwitz; Carolin Bast; Sophie Stefanjuk; Sophia Ruckriegl;
Evangelos Prokakis; Carsten Gründker; Julia Gallwas
Department of Gynecology and Obstetrics, University Medical Center
Göttingen, Göttingen, Deutschland
Background: Every year, over 12 000 and 4500 new cases of endome-
trium and cervical carcinoma (EC and CC) are diagnosed in Germany,
respectively. Despite signicant advances in disease management, over
4500 women still succumb yearly to EC or CC. Furthermore, therapies
frequently imply a poorer life quality and a loss of fertility for women of
reproductive age. Previous studies from our group and others demon-
strated an important tumor supportive function of the Histone 2B
monoubiquitination (H2Bub1) epigenetic mark and its E3-Ligase com-
plex (RNF20/RNF40) in several cancers like HER2-positive breast cancer
or colorectal carcinomas. Interestingly, the function of H2Bub1 in EC and
CC has not yet been investigated.
Methods: We took advantage of patient data from e Cancer Atlas
Genome (TCGA) to investigate the potential implication of RNF20 and
RNF40 expression in EC and CC aggressiveness. We next performed in
vitro functional assays to assess the consequence of RNF20 or RNF40 loss
in EC and CC cells. Finally, we ran whole transcriptome analyses to iden-
tify the molecular mechanisms underlying H2Bub1 tumor-supportive
function in CC.
Results: Survival analyses demonstrated that high RNF20 and RNF40
expression correlate with poor prognosis for CC patients but not EC
patients. In line with these ndings, we identied a strong dependency
of CC cells but not EC cells to the H2Bub1-signaling axis in vitro. Our
mRNA-sequencing analysis upon RNF40 knockdown established an
important role of the H2Bub1 signaling supporting epithelial to mesen-
chymal transition and consequently oncogenic properties of CC cells.
Discussion: Our results identied for the rst time H2Bub1 epigene-
tic gene regulation as a central signaling pathway of CC malignancies.
Interestingly, this nding could not be extended to EC entities, underlying
the context specicity of molecular mechanisms driving the aggressive-
ness of cancers.
Conclusion: Targeting the enzymatic activity of the RNF20/RNF40-
complex could represent an attractive opportunity for the development of
novel anti-CC therapies.
Disclosure Statement: e authors declare no conict of interest.
636
OVARIO, A Phase 2 Study of Niraparib + Bevacizumab in
Advanced Ovarian Cancer (OC) Following Front-Line Platinum-
Based Chemotherapy (CT) with Bevacizumab (bev): Updated
Analysis
Melissa. M. Hardesty1; Jacek Grabowski2; Thomas Krivak3; Gail. S. Wright4;
Erika Hamilton5; Evelyn. L. Fleming6; Jimmy Belotte7; Erika Keeton7; Ping
Wang7; Aine Clements8; Heidi. J. Gray9; Gottfried. E. Konecny10; Richard. G.
Moore11; Debra Richardson12
1Alaska Womens Cancer Care, Anchorage, USA
2Department of Gynecology, Campus Virchow Clinic, Charité Comprehensive
Cancer Center (CCCC), Charité Medical University Berlin, Berlin, Deutschland
3Division of Gynecologic Oncology, Department of Obstetrics and Gynecology,
The Western Pennsylvania Hospital, Pittsburgh, USA
4Florida Cancer Specialists and Research Institute, New Port Richey, USA
5Medical Oncology, Tennessee Oncology, Sarah Cannon Research Institute,
Nashville, USA
6Division of Gynecologic Oncology, Norris Cotton Cancer Center, Dartmouth-
Hitchcock Medical Center, Lebanon, USA
7GlaxoSmithKline, Waltham, USA
8Department of Gynecologic Oncology, Riverside Methodist Hospital,
Columbus, USA
9Division of Gynecologic Oncology, Department of Obstetrics and Gynecology,
University of Washington, Seattle, USA
10University of California Los Angeles, Los Angeles, USA
11Division of Gynecologic Oncology, Department of Obstetrics and Gynecology,
Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, USA
12Division of Gynecologic Oncology, Stephenson Cancer Center, University of
Oklahoma Health Sciences Center, Oklahoma City, USA
Background: Niraparib improved PFS vs placebo in patients (pts) with
newly diagnosed, advanced OC with response to platinum in the PRIMA
trial; niraparib + bev improved PFS vs niraparib in platinum-sensitive
recurrent OC. OVARIO is a single-arm, open-label study evaluating
niraparib + bev treatment aer response to rst-line (1L) platinum-based
CT + bev.
Methods: Eligible pts had newly diagnosed high-grade serous or endo-
metrioid stage IIIB–IV OC with CR, PR, or no evidence of disease aer
1L platinum-based CT + bev; pts could have received neoadjuvant CT or
primary debulking surgery. Tissue testing for homologous recombination
(HR) status was completed at enrollment. Pts received niraparib 200 or
300 mg QD (based on body weight/platelet count) for up to 3 y + bev
15 mg/kg Q3W for up to 22 cycles (including with 1L CT). Endpoints
included 18-mo PFS rate (primary), PFS, OS, safety, tolerability, and
change from baseline in the Functional Assessment of Cancer erapy–
Ovarian Symptoms Index (FOSI) score.
Results: is analysis included 105 pts. At data cuto (June 16, 2021),
median follow-up was 27.6 mo (95% CI 25.5–27.7). Overall, median PFS
(mPFS) was 19.6 mo (95% CI 16.5–25.1). In the HR-decient (HRd) pop-
ulation (n=49), mPFS was 28.3 mo (95% CI 19.9–non-estimable [NE]).
mPFS was 28.3 mo (95% CI 12.1–NE) in the HRd/BRCA-wild-type pop-
ulation (n=16) and NE in the HRd/BRCA-mutant population (n=29). In
the HR-procient population (n=38), mPFS was 14.2 mo (95% CI 8.6–
16.8). e 24-mo PFS rates will be presented at the meeting. In the overall
population, OS was immature with an event rate of 23.8%. FOSI baseline
mean (SD) score was 25.7 (3.79) with a least square mean change from
baseline of −0.7 (95% CI −1.4–0).
Discussion: Niraparib + bev showed promising ecacy following 1L plat-
inum-based CT, with no clinically meaningful impact on quality of life as
assessed by FOSI.
Conclusions:Niraparib + bev 1L maintenance demonstrated promising
results in advanced OC.
Disclosure Statement: e authors declare the following: Funding: GSK study
213358; NCT03326193. Previously presented at SGO 2022, USA (abstract 170);
submitted with permission of authors.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 113
Poster
42
Neoadjuvant chemotherapy followed by radical surgery
Patients with locally advanced cervical carcinoma in the FIGO
stage IIIb-IVa
Hala Allakeh1; Wladimir Pauker2; David Lazica3; Hilko Strehl4
1DIAKONIEKLINIKUM, Frauenklinik, Assistenzärztin, Rotenburg (Wümme),
Deutschland
2DIAKONIEKLINIKUM, Frauenklinik, Chefarzt, Rotenburg (Wümme), Deutschland
3DIAKONIEKLINIKUM, Urologische Klinik, Chefarzt, Rotenburg (Wümme),
Deutschland
4DIAKONIEKLINIKUM, Strahlenklinik, Chefarzt, Rotenburg (Wümme),
Deutschland
Aim: e locally advanced cervical carcinoma St. III & IV according to
FIGO - selected patients benet from neoadjuvant chemotherapy with
subsequent radical surgery compared to chemoradiotherapy alone.
Methods: three patients with locally advanced cervical cancer were
treated within one year. e patients had histologically clear squamous
cell carcinoma of the cervix uteri, which inltrated the entire cervical
stroma, upper third of the vagina, urinary bladder and parametria on
both sides, up to the pelvic wall and with intra-abdominal suspected of
malignancy LN and hydronephrosis and corresponded to FIGO stage IIIb
and IVa. e patients received 3 cycles of neoadjuvant chemotherapy with
carboplatin (AUC 5) / paclitaxel (175 mg / m2) every three weeks. Aer
down-staging, all patients with a good clinical response to NACT under-
went an interdisciplinary radical operation.
Results: Aer NACT there was a clear improvement in the results with
regard to the reduction in tumor volume, so that all 3 patients were oper-
ated on. One received a radical extended hysterectomy according to Piver
III and the other two according to Piver IV with partial resection of the
urinary bladder and the distal part of the right ureter as well as pelvic and
para-aortic lymphadenectomy. e pathological ndings of the surgical
specimens showed the resected tumor with free resection margins and
tumor-free pelvic and para-aortic lymph nodes. e intra- and postop-
erative time was uncomplicated. e patients then received 6 cycles of
chemoradiotherapy with cisplatin. Aer a mean follow-up of 12 months
(range: 12-24), all patients were free of recurrences and there was no evi-
dence of local pelvic complications.
Summary: e treatment for cervical local advanced cancer in the last
two decades have seen many dierent therapy modalities and what is opti-
mal treatment still controversial. Neoadjuvant chemotherapy followed by
radical surgery for locally advanced cervical CA is a practicable therapeu-
tic strategy with good short- and long-term results in selected patients.
Disclosure Statement: e authors declare no conict of interest.
109
Modied operative therapy for locally advanced vulvar cancer
Wladimir Pauker1; Hala Allakeh1
1AGAPLESION Diakonieklinikum Rotenburg, Frauenklinik, Rotenburg,
Deutschland
Background: modied plastic covering of the vulvar defect aer radical
vulvectomy in locally advanced vulvar cancer to reduce postoperative
wound healing disorders.
Methods: Within two years, 23 patients, mean age 77 years, with locally
advanced vulvar cancer were treated surgically. e patients had histo-
logically conrmed squamous cell carcinoma of the vulva from FIGO
IB (associated / not associated HPV). All tumors were in the area of the
anterior vulva or multifocal as from FIGO IB.Patients receive either a par-
tial or a complete vulvectomy with a modied VU advancement ap as
well as inguinofemoral LNE or sentinel lymphonodectomy on both sides.
edefect covering in the area of the anterior vulva and clitoral region
or the cranial labia minora as a V-shaped drawing of the ap was moved
caudally and sewn in aer the aps had been removed. e defect at the
mons pubis was moved caudally even aer mobilization and thus sutured.
is results in the U-shape compared to the VY advancement ap.
Result: e surgical results with this ap technique for the treatment of
the selected patients are promising: R0 resection of the vulvar cancer, no
postoperative complication rate, so far free of local recurrences and a high
level of patient satisfaction.
Discussion: Especially with oncological indications, it is essential to be
able to treat the oen larger defects aer the histologically conrmed
Intoto-excision of malignant vulvar tumors by means of plastic-recon-
structive surgical procedures.
Conclusion: is technique is very demanding and should be performed
by an experienced surgeon, then based on previous experience, a mini-
mum of postoperative complications can be expected.
Disclosure Statement: e authors declare no conict of interest.
118
The presence of regulatory T-cells and their chemoattractant
CCL22 in endometrial cancer in correlation with overall
survival
Mareike Mannewitz1; Susanne Beyer1; Laura Hahn1; Sarah Meister1;
Konstantin Schnell2; Carolin Perleberg2; David Anz2; Elisa Schmöckel1,3;
Alexander Burges1; Sven Mahner1; Udo Jeschke4; Mirjana Kessler1;
Stefanie Corradini5; Fabian Trillsch1; Thomas Kolben1
1Department of Obstetrics and Gynecology, University Hospital, LMU Munich,
München, Deutschland
2Division of Clinical Pharmacology, University Hospital, LMU Munich, Center of
Integrated Protein Science Munich, München, Deutschland
3Institute of Pathology, University Hospital, LMU Munich, München, Deutschland
4Department of Obstetrics and Gynecology, University Hospital Augsburg,
Augsburg, Deutschland
5Department of Radiation-Oncology, University Hospital, LMU Munich,
München, Deutschland
Background: In Endometrial carcinoma (EC) therapy immunothera-
peutic strategies gain more and more attention. Recruitment of tumor
inltrating regulatory T-cells (Treg) has been shown to have prognos-
tic relevance in a variety of tumor entities by evading the host immune
response. e chemokine CCL22 has been reported as a major attractant
for Treg. Aim of this study is to clarify the mechanistic role and potential
prognostic signicance of CCL22 secretion and Treg in EC.
Methods: A panel of 275 specimens of EC was screened immunohistochem-
ically for the presence of FoxP3+ Treg and CCL22. Immunouorescence
double staining for CCL22 and dierent immune cell markers was per-
formed. Further, a set of functional assays was conducted using the EC cell
lines Ishikawa+ and RL95-2 aer coculturing with isolated Treg in order
to assess their inuence on tumor cell behaviour.
Result: Our results showed that an increased inltration of regulatory
T-cells was associated with reduced overall survival (OS). Coculture of
EC tumor cells with Treg led to an enhanced invasion, migration, and
viability of the tumor cells. High CCL22 staining in tumor cells and the
presence of isolated immune cells in tumor distant areas resulted in a
signicantly increased OS for patients. ese immune cells were charac-
terized as CD68+ and CD80+, concluding they were M1 macrophages.
Conversely a moderate, secretory-appearing staining in the peritumoral
and intratumoral stroma with a worse prognosis.
Discussion: Treg are associated with poorer outcome in women with EC.
e impact of Treg on tumor cell behaviour, favouring especially invasion
and migration, supports the hypothesis that increased levels of FoxP3+
Treg in the tumor microenvironment may promote tumor growth.
Furthermore, our study is the rst investigation of CCL22 in EC and indi-
cated that CCL22 was associated with OS in dependence on its location
and its producing cell type.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts114
Conclusion: Our results provide evidence of Treg as a possible therapeu-
tic target in EC. e impact of CCL22 regarding its dierent localisations
should further be investigated.
Disclosure Statement: e authors declare no conict of interest.
132
Sialyl Lewis X, Sialyl Lewis A and Lewis Y as prognostic factors
in endometrial and cervical cancer
Lena Mueller1; Sophie Mitter1; Mareike Mannewitz1;
Lucia Katharina Keilmann1; Sarah Meister1; Theresa Kolben1;
Elisa Schmoeckel2; Alexander Burges1; Fabian Trillsch1; Bastian Czogalla1;
Udo Jeschke1,3; Mirjana Kessler1; Sven Mahner1; Thomas Kolben1;
Susanne Beyer1
1LMU Munich, University Hospital, Department of Obstetrics and Gynecology,
München, Deutschland
2LMU Munich, University Hospital, Institute of Pathology, München, Deutschland
3University Augsburg, University Hospital, Department of Obstetrics and
Gynecology, Augsburg, Deutschland
Background: Cervical and endometrial cancers are common cancers
worldwide. Several risk factors have been identied and treatment has
been improved in recent years. However, in advanced stages, therapeuti-
cal options are still limited. It has been reported that the expression of the
blood group antigens Sialyl Lewis X (SLeX), Sialyl Lewis A (SLeA) and
Lewis Y (LeY) is associated with prognosis in several tumors like breast
cancer.1 Large studies on endometrial and cervical cancer are still missing.
Methods: 234 patients with endometrial cancer (EC) and 244 with cervi-
cal cancer (CC) were included. Specimens were immunohistochemically
stained with antibodies for SLeX und SLeA and LeY. Expression was cor-
related to histopathological variables.
Result: In EC, increased SLeX expression correlated signicantly with
lower pT-stage (p=0.013), low grading (p<0.001), low FIGO-status
(p=0.006) and better overall survival (p= 0.023). High IRS of LeY was
correlated with lower grading (p=0.005) and positive pN (p=0.038) and
worse progression free survival (p=0.022). SLeA expression was higher at
lower pT stage (p=0.013), low grading (p=0.002) and better progression
free survival (p=0.043).
In CC, similar tendencies were shown, but they were not signicant in the
overall collective. However high SLeX expression was signicantly cor-
related with low grading (p=0.029) and pN+ (p=0.032) in patients with
adeno(-squamous) cervical cancer. In squamous cell tumors high LeY
correlated signicantly with better overall (p=0.010) and progression free
survival (p=0.013). No signicant correlation was detected for SLeA.
Discussion and Conclusion: Especially in endometrial cancer, SLeX,
SLeA and LeY were correlated to histopathological parameters and to sur-
vival rates. ese results underline the importance of these blood antigens
as markers for endometrial cancer. Further studies are needed to investi-
gate the underlying processes.
Reference:
1 Jeschke, U. et al. 2005. ‘Expression of sialyl lewis X, sialyl Lewis A, E-cadherin
and cathepsin-D in human breast cancer […]’, Anticancer Res, 25: 1615–22.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
291
SCOUT-1: prospective non-interventional study in BRCA/HRD
tested ovarian cancer (OC) patients eligible for 1L-platinum-
based chemotherapy - Trial in progress
Klaus Pietzner2; Elena Ioana Braicu1; Regina Glowik2; Matthias Rose3;
Pauline Wimberger4; Jalid Sehouli1
1North-Eastern German Society of Gynecological Oncology (NOGGO) and
Department of Gynecology with Center for Oncological Surgery, Charité
University Medicine of Berlin, Campus Virchow Klinikum, Berlin, Deutschland
2AstraZeneca, Wedel, Deutschland
3Center for Internal Medicine and Dermatology, Department of Psychosomatic
Medicine, Charité-Universitätsmedizin Berlin, Berlin, Deutschland
4Department of Gynecology and Obstetrics, TU Dresden and National Center for
Tumor Diseases (NCT/UCC), Dresden, Deutschland
Background: Two third of patients with OC, have an advanced stage at ini-
tial diagnosis accompanied with poor prognosis. Results from landmark
trials of maintenance therapy (MTX) with poly ADP ribose polymerase
inhibitors (PARPi), especially in tumors associated with homologous
recombination deciency (HRD), like BRCA-mutated tumors, led to the
strong recommendation on testing and treatment procedures in the clini-
cal routine in patients with advanced high-grade epithelial OC. e trans-
lation of these guidelines into clinical routine aects care management
and therefore needs to be evaluated.
Methods: SCOUT-1 is a German prospective, observational study
(NCT04830709; NOGGO ov54) to collect clinical real-world and
patient-reported outcome (PRO) data in patients newly diagnosed with
histologically conrmed advanced (FIGO stage III or IV) high-grade epi-
thelial ovarian, fallopian-tube, or primary peritoneal cancer. Selection cri-
teria include written informed consent, completed surgery (if applicable),
eligible for platinum-based chemotherapy, BRCA1/2 mutation tested and
willingness/ability to report PROs electronically. About 750 patients are
planned to be included in up to 80 hospitals or oce-based sites. Patients
will be followed up for a maximum of 7 years. e primary objective is to
determine the eectiveness of standard treatment sequences by estimating
progression-free survival according to investigator’s assessment. Further
focus is to describe biomarker-testing algorithm, patient selection and to
assess patients’ QoL, symptoms, needs, as well as patients’ expectations.
First subject was included in the study in June 2021. Primary completion
date is planned in Q2 2032.
Indication of source:
1. Presented at 22nd European Congress on Gynecological Oncology (ESGO)
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
294
Alternative sentinel methods in patients with vulvar cancer
Farnaz Jakubek1; Mandy Mangler1; Katharina Vasiljeva1; Joyce
Pullankavunkal1; Natalia Papadopoulos1; Malgorzata Lanowska1
1Vivantes, Gynäkologie, Berlin, Deutschland
Background: In recent studies sentinel lymphonodectomies have been
found to be a feasible method to treat patients with vulvar cancer. Sentinel
detections have been applied in many cancer entities to establish individ-
ualised and targeted concepts in the treatment of cancer patients. Tracing
agents are mostly limited to blue dye only, technetium only, blue dye plus
technetium combined. Agents that have been identied recently have not
yet found their way into national guidelines.
Methods: We describe a case series of 10 patients with vulvar cancer and
sentinel detection with indocyanine green. In all patients sentinel detec-
tion was performed with technetium nanocolloid and blue dye, according
to the conventional protocol described in the national cancer guidelines.
Additionally we applied indocyanin green locally in the vulva to compare
the detection rates.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 115
Results: Indocyanin tracers were easy to apply, the tracers appeared in
the groin lymph nodes within 20-46 minutes aer the application. Near-
infrared uorescence cameras were needed to detect the lymphnodes.
Indocyanin was superior to blue dye in the detection of sentinel nodes.
Discussion: Sentinel lymph node dissection in vulvar cancer patients are
limited, partially due to complicated applications with radioactive agents.
Indocyanine green SLN mapping in vulvar cancer is a new method, with
yet though limited evidence to further individualise and simplify opera-
tive therapy in these women.
Conclusion: Indocyanin is easy to apply, requires no help of radiother-
apists, as it is not radioactive. It has very few side eects and is thus a
feasible alternative to conventional technetium-99m nanocolloid tracers.
Detection rates seem to be superior to the application of blue dye only.
Disclosure Statement: e authors declare no conict of interest.
302
NOGGO ov-42/MAMOC: Rucaparib MAintenance after
Bevacizumab Maintenance following Carboplatin based rst
line chemotherapy in Ovarian Cancer patients
Jalid Sehouli1,2,3; Pauline Wimberger4,5,6,7 8; Jessica Dysarz3;
Angela Relógio9,10; Jens Gerber11; Eva Egger12; Michael Eichbaum13;
Ralf Witteler14; Mustafa Deryal15; Klaus Pietzner1; Radoslav Chekerov1;
Elena Ioana Braicu1,3
1Charité Universitätsmedizin Berlin, Department of Gynecology, Berlin,
Deutschland
2Charité Universitätsmedizin Berlin, European Competence Center for Ovarian
Cancer (EKZE), Berlin, Deutschland
3Nord-Ostdeutsche Gesellschaft für Gynäkologische Onkologie (NOGGO) e.V.,
Berlin, Deutschland
4Technische Universität Dresden, Department of Gynecology and Obstetrics,
Dresden, Deutschland
5Technische Universität Dresden, Faculty of Medicine and University Hospital
Carl Gustav Carus, Dresden, Deutschland
6Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Deutschland
7National Center for Tumor Diseases (NCT/UCC), Dresden, Deutschland
8German Cancer Research Center (DKFZ), Heidelberg, Deutschland
9Institute for Systems Medicine and MSH-Medical School Hamburg, Hamburg,
Deutschland
10Charité Medical University of Berlin, Institute for Theoretical Biology and
Molecular Cancer Research Center, Berlin, Deutschland
11Städtisches Klinikum Dessau, Clinic for Gynecology and Obstetrics, Dessau-
Roßlau, Deutschland
12Universitätsklinikum Bonn, Department of Gynaecology and Gynaecological
Oncology, Bonn, Deutschland
13Helios Dr. Horst Schmidt Kliniken Wiesbaden, Department of Gynecology and
obstetrics, Wiesbaden, Deutschland
14Universitätsklinikum Münster, Clinic for Gynecology and Obstetrics, Münster,
Deutschland
15CaritasKlinikum Saarbrücken St. Theresia, Center for gynecology, Saarbrücken,
Deutschland
Background: Most ovarian cancer (OC) patients are diagnosed in
advanced stages. Debulking surgery, followed by platinum-based chemo-
therapy and bevacizumab (bev), followed by bev maintenance therapy,
is a therapeutical option for advanced BRCA wild type (BRCAwt) OC
patients in Germany. Despite that 70% of the patients will relapse within
2 years aer diagnosis, prolongation of maintenance therapy might be an
option to improve PFS. Current data showed that bev given longer than
15 months do not translate in better PFS. erefore, in this clinical trial
we aim to analyze the role of sequential maintenance with bev followed
by rucaparib vs bev alone in BRCAwt high grade OC patients. NOGGO
Ov-42/MAMOC trial (NCT04227522) is a phase 3, randomized, place-
bo-controlled study evaluating rucaparib maintenance following bevaci-
zumab maintenance for the treatment of advanced primary high grade
BRCAwt OC.
Methods: 190 BRCA wt patients with histologically conrmed advanced
(FIGO stage IIIA- IV of the 2014 FIGO classication) high grade serous
or high grade endometrioid OC, fallopian tube cancer, primary perito-
neal cancer or clear cell carcinoma of the ovary will be randomized 2:1 to
receive either rucaparib 600mg BID or placebo as maintenance therapy
following rst line chemotherapy with 6 cycles of Carboplatin/Paclitaxel
and at least 12 months of bev given together with chemotherapy and
as maintenance. Randomization is stratied by surgery planned time-
point (neoadjuvant vs. adjuvant), surgical outcome (no residual tumor
massvs. residual tumor mass), response to chemotherapy + bev (CR/
NED vs. PR/SD) and study center. Treatment will continue for 24 months
or until disease progression, unacceptable toxicity, or withdrawal, what-
ever occurs rst. Primary endpoint is PFS per RECIST v1.1. Secondary
endpoints are PFS2, quality of life (EORTC QLQ-C30/OV28, FSI, SF-12,
PROC-CTCAE, Everyday Memory Questionnaire), daily activity, time to
next medical intervention, time to next subsequent therapy, safety assess-
ments and OS. At the moment 14 patients are randomized.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
346
Gynecological cancer patients and their health care
infrastructure during the corona pandemia in Berlin in
2020/21
Malgorzata Lanowska1; Katharina Vasiljeva1; Joyce ; Pullankavunkal1;
Farnaz Jakubek2; Vera Prugger2; Natalia Papadopoulos3; Mandy Mangler2
1Vivantes, Gynäkologie, Berlin, Deutschland
2Vivantes, Gynäkologie, Berlin, Deutshcland
3Vivantes, Gynäkologie, Berlin, Deutschland
Background: Severe unstableness has occurred during the Covid pan-
demic in 2020/21 regarding the accessibility of health care structures.
Patients with symptoms did either not consult their gynecologists, or were
not able to get access to their gynecologists, due to canceled outpatient
consultation hours.
Methods: e rst lockdown due to Covid-19 in Berlin occured in March
2020. We compared the cancer data and cancer patients consultation to
three gynecological centers in three academic hospitals in Berlin in the
years 2018/2019 to 2020/2021. Consultations and stages of tumors in 840
patients were compared and matched monthly between the years.
Result: In the rst lockdown March 2020- June 2020 20% less cancer
patients consultated our clinics. e results were found to be signicant.
Elder patients did tend to consult the health care system less during the
lockdown as compared to before the lockdown.
In the rst lockdown March 2020- June 2020 20% less cancer patients con-
sultated our clinics. e results were found to be signicant. Elder patients
did tend to consult the health care system less during the lockdown as
compared to before the lockdown.
Aer the rst lockdown a tendency to more advanced cancer stages were
observed in the cancer patients.
Discussion: During the Covid-19 pandemic medical care for cancer
patients was impaired, as compared to the time before the pandemic.
Signicantly less patients consulted the health care system and found sup-
port for their symptoms.
Conclusion: e alterations due to the pandemic will, most probably,
aect the long term survival of these cancer patients.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts116
347
Expression of the adipokine chemerin and its receptor
chemokine-like receptor 1 (CMKLR1) in ovarian cancer
Susanne Schüler-Toprak1; Florian Weber2; Christa Büchler3;
Olaf Ortmann1; Oliver Treeck1
1Department of Gynecology and Obstetrics, University Medical Center
Regensburg, Regensburg, Deutschland
2Department of Pathology, University of Regensburg, Regensburg, Deutschland
3Department of Internal Medicine I, University Medical Center Regensburg,
Regensburg, Deutschland
Background: e multifunctional adipokine chemerin plays an import-
ant role in several cancer types. Here, we investigated the role of chemerin
and its receptor CMKLR1 in ovarian cancer (OC). Protein expression of
chemerin and CMKLR1 in OC was assessed and correlated with OC mark-
ers, steroid hormone receptors and cancer-associated genes. Additionally,
we examined the inuence of the expression of chemerin and its receptor
on survival of OC patients.
Methods: For this purpose, we established a tissue microarray from 153
OC patients and performed immunohistochemical analyses.
Result: Chemerin was found to positively correlate with progesterone
receptor (p<0.0001), CEA (p=0.0428), as well as with nuclear and cyto-
plasmic estrogen receptor β; (p=0.0213 and p=0.0029, respectively)) in
serous OCs. Moreover, a strong positive correlation was found between
chemerin and estrogen related receptors (ERR) α, β and γ (p< 0.0001,
p=0.0007 and p< 0.0001, respectively) in all OCs as well as in the serous
subtype. Also CMKLR1 was shown to strongly correlate with expression
of ERR α, β and γ in all OC cases and in the serous subtype. Survival
analyses revealed that chemerin expression did not aect overall (OS) or
progression-free survival of OC patients. However, higher expression of
CMKLR1 in low grade OCs indicated signicantly decreased OS com-
pared to those with lower levels of CMKLR1 (p<0.05).
Discussion: Our data underline a role of chemerin and its receptor in OC
development as we observed correlations of chemerin with the expression
of several steroid receptors and OC markers as well as an association of
CMKLR1 with survival.
Conclusion: Our data suggest an important role of chemerin and its
receptor in OC.
Disclosure Statement: e authors declare no conict of interest.
351
Precancerous lesions in patients with abnormal PAP smear
Malgorzata Lanowska1; Vera Prugger2; Natalia Papadopoulos1;
Katharina Vasiljeva1; Farnaz Jakubek2; Joyce Pullankavunkal1;
Mandy Mangler2
1Vivantes, Gynäkologie, Berlin, Deutschland
2Vivantes, Gynäkologie, Berlin, Deutschland
Background: e appearance of precancerous lesions of the cervix due
to HPV infection is known to be related to pathological ndings in pap
smears. Pap smears are classied in ve dierent groups Pap I-V.
Inconsistent results between pap smears and histological ndings trouble
the reliability of pap smears.
Methods: Data of 1500 patients who were referred to our oncological cen-
ter in 2020 and 2021 to undergo colposcopy and pathological validation
due to pathological pap smears or HPV infection was analysed.
Results: Pap smears were correlated with histopathological dysplasia to
dierent extents: in high grade dysplasia 14% of patients showed unsus-
picious or slightly changed pap smear results: Pap I 5.8%, Pap IIg,p,e in
8.3%. e rest 86% was unevenly spread. Pap IIIp was found in 11,2%, Pap
IIID1 in 16,1%, Pap IIID2 in 33,9% of the women.
Pap IV, commonly directly correlated to high grade dysplasia, could only
be proven in 20% of the pap smears analysed: Pap Iva-p 19.5% and Pap
IVb-p 1.7%
Discussion: Pap smears are used as a screening method in Germany to
detect low and high grade lesions and cervical cancer. ese pap smears
seem to have an inconsistent reliability to nd histological precancerous
lesions.
Conclusion: us, PAP smears alone have a low prediction rate for the
presence of dysplasia and should be combined with other methods before
initiating therapy.
Disclosure Statement: e authors declare no conict of interest.
397
iKNOW - Development and evaluation of an online tool for
counseling BRCA1/2 mutation carriers
Caren Hilger1; Friederike Kendel1; Maren Heibges2; Christine Schmid2;
Markus Feufel2; Dorothee Speiser3
1CharitéUniversitätsmedizin Berlin, Geschlechterforschung in der Medizin
(GiM), Berlin, Deutschland
2Technische Universität Berlin, Institut für Psychologie und Arbeitswissenschaft,
Fachgebiet Arbeitswissenschaft, Berlin, Deutschland
3CharitéUniversitätsmedizin Berlin, Klinik für Gynäkologie mit Brustzentrum,
Zentrum Familiärer Brust- und Eierstockkrebs, Berlin, Deutschland
Background: Women carrying BRCA1/2 gene mutations have markedly
increased lifetime risk of breast/ovarian cancer. Medical consultation
poses challenges for physicians and women seeking advice: Physicians
have to communicate complex information in a comprehensible way to
enable preference sensitive decisions. Women need to understand their
individual cancer risks to make informed decisions to achieve optimal
risk management.
Aim: We developed the evidence-based online counseling tool iKNOW to
support consultation of BRCA mutation carriers in direct doctor-patient
conversation and as individual reference book for counselees.
Method: In an RCT, participants received either counseling using iKNOW
or standard consultation. At four measuring points (T0=before consulta-
tion; T1=immediately aerwards; T2=four weeks; T3=six months aer
consultation), participants received self-report questionnaires including
items on risk understanding. χ2-tests and robust Mann-Whitney U-tests
were used to compare participants in the intervention group with the con-
trol group.
Results: At baseline, N=220 women participated in the study. Of those,
n=108 were counseled using iKNOW, n=112 received standard con-
sultation. Of the total sample, 140 women (63.6%) were BRCA1 carriers
and 80 (36.4%) carried a pathogenic variant in BRCA2. e distribution
did not dier between intervention and control group. Data collection is
currently ongoing and will be completed in October 2021. Results on risk
understanding can be presented in 2022.
Outlook: If evaluation is successful, the counseling tool will be adopted
into standard care and its content can be regularly adapted to current
evidence.
Disclosure Statement: e authors declare no conict of interest.
398
Impact of COVID-19 pandemic on the treatment of cervical
cancer in Hessian hospitals– a population-based study
Petra Neuser1; Heiko Müller2; Anne Byl3; Nora Bamberger3; Martin Rapp3;
Soo-Zin Kim-Wanner1
1Hessisches Krebregister, Hessisches Landesprüfungs- und Untersuchungsamt
im Gesundheitswesen, Landeauswertungsstelle, Frankfurt, Deutschland
2HA Hessen Agentur GmbH, Wiesbaden, Deutschland
3Hessisches Krebsregister, Vertrauensstelle, Frankfurt, Deutschland
Background: During the Covid-19 (Cov19) pandemic hospitals were
assigned to four levels according their resources to manage the increased
demand of intensive care treatments. is study aims to contribute
towards quantifying the impact of the Cov19 pandemic on cancer care of
patients with cervical cancer in Germany by investigating the diagnoses
and treatments in Hessian hospitals of dierent Cov19 levels.
Methods: Data of patients with cervical cancer (C53) diagnosed from
2016 to 2020, were extracted from the database of the Hessian cancer
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 117
registry. With regard to a continuously stable registration activity eleven
hospitals were included in the analysis. Seven hospitals met the criteria for
Cov19 level 1 (highest requirements) and four hospitals for level 2.
Result: In 2020, 31% fewer patients with cervical cancer were diag-
nosed in eleven Hessian hospitals compared to previous years (n=124 vs.
n=179). Primary tumor resections were reduced by 24%, whereas no dif-
ference could be detected in their relative amount or timespan from diag-
nosis. e patient cohort was younger with a median age of 46 vs. 50 years
and with early stage I-II in 70% vs. 62%. e reduction in treatment was
mostly seen in the Cov19 level 1 hospitals, while level 2 hospitals could
increase the amount of diagnosed (14%) and treated (27%) patients.
Discussion: Despite a reduction of diagnoses and treatments, primary
surgery was not delayed. e patient characteristics imply that predomi-
nantly elder women with advanced stages omitted hospital treatment. e
increased burden of care of Cov19 patients for the level 1 hospitals clearly
had an impact on the care of cancer patients, which could be partially
absorbed by level 2 hospitals.
Conclusion: Reorganisation of hospitals according to Cov19 levels was an
important tool to enable treatment of Cov19 patients while maintaining
cancer care by shiing treatment to other hospitals. However, there is an
impact on missed diagnoses and treatments of patients, that will result in
a higher morbidity and mortality.
Disclosure Statement: e authors declare no conict of interest.
565
The Role of DAPK1 in the Cell Cycle Regulation of Cervical
Cancer Cells and in Response to Topotecan
Khayal Gasimli1; Monika Raab1; Sven Becker1; Mourad Sanhaji1;
Klaus Strebhardt1,2
1Universitätsklinikum Frankfurt, Gynäkologie und Geburtshilfe, Frankfurt am
Main, Deutschland
2Deutsches Krebsforschungszentrum, Partner facility Frankfurt, Frankfurt,
Deutschland
Introduction/Background:Cervical cancer is one of the most serious
health conditions, with nearly 500,000 women developing the disease
each year worldwide. At present, the treatment of recurrent cervical can-
cer remains largely ineective, and eorts in cancer drug development are
currently focused on critical serine/threonine kinases, such as death-as-
sociated protein kinase 1 (DAPK1) and polo-like kinase 1 (PLK1). In the
current study, we aimed at exploring the cell cycle roles of DAPK1 and
PLK1 in cervical cancer cells.
Methods: Multiple methods including western blotting and assays were
used for studying kinase activity, apoptosis, cell cycle, cell proliferation,
immunouorescence and proximity ligation.
Result(s):e present study demonstrated that, in cervical cancer cells, the
enzymatic activity of DAPK1 was regulated in a cell cycle-specic man-
ner. NIMA-related kinases, CDKs, PLKs and Aurora kinases regulate the
function of centrosomes by orchestrating the separation of chromosomes
during cell division. e present study added DAPK1 to this group of pro-
tein kinases due to its localization at centrosomes during mitosis. It was
shown that DAPK1 was autophosphorylated at Ser308 in the G2phase and
during mitosis. From prophase to metaphase, the colocalization of PLK1
and DAPK1 at centrosomes was observed. Furthermore, the interaction of
both these kinases could be demonstrated using proximity ligations assays
and immunoprecipitations. DAPK1 was found to be a substrate of PLK1.
Topotecan is an eective drug used for the treatment of cervical cancer.
Conclusion:e current study examined the role of DAPK1 in topote-
can-induced cervical cancer cell death, and it was identied that RNA
interference-based silencing of DAPK1 decreased the apoptotic eect of
topotecan. us, these ndings suggested that DAPK1 could be a bio-
marker and a potential target for the response to topotecan during the
therapy of patients with cervical cancer.
Disclosure Statement: e authors declare no conict of interest.
571
RIG-I as a potential new target for immunotherapies in
endometrial cancer
Sophie Mitter1; Lena Müller1; Mareike Mannewitz1; Sarah Meister1;
Theresa Kolben1; Elisa Schmoeckel2; Alexander Burges1; Bastian Czogalla1;
Anna Hester1; Sven Mahner1; Udo Jeschke1,3; Stefanie Corradini4;
Fabian Trillsch1; Mirjana Kessler1; Thomas Kolben1; Susanne Beyer1
1Department of Obstetrics and Gynecology, University Hospital, LMU Munich,
Germany
2Institute of Pathology, University Hospital, LMU Munich, Germany
3Department of Obstetrics and Gynecology, University Hospital Augsburg,
Augsburg, Germany
4Department of Radiation-Oncology, University Hospital, LMU Munich, Munich,
Germany
Background: RIG-I (retinoic acid inducible gene I) increases expression
and secretion of type-I-interferons, leading to recruitment of immune
cells and induction of apoptosis. RIG-I is attributed a tumor-suppressive
eect in various tumor entities such as melanoma. For endometrial cancer
(EC), one of the most common gynecological malignancies and an immu-
nogenic cancer, data about RIG-I as part of the innate immune system are
missing. Our aim is to investigate the relationship between RIG-I expres-
sion and outcome in patients with EC.
Methods: Immunohistochemical staining was performed on 225 spec-
imens of patients with EC. RIG-I expression was correlated with histo-
pathological and survival data.
Result: Elevated RIG-I levels correlated positively with advanced tumor
stage and poor grading (FIGO stage p=0.027; T stage p=0.010; grading
p=0.007). Overall survival was shorter in patients with high RIG-I levels
(p=0.009). Furthermore, RIG-I was found to be an independent negative
predictor of progression-free survival (p=0.022).
Discussion and Conclusion: Our data establish RIG-I as a new marker
for outcome in patients with EC. Compared to most other tumor entities
where RIG-I seems to be tumorsuppressive, higher RIG-I-expression is
associated with exactly the opposite eect in EC. In further studies, we are
investigating the underlying mechanisms in more detail.
Disclosure Statement: e authors declare no conict of interest.
580
Targeting of the Polo-like kinase 1 (PLK1) to improve the
eciency of Olaparib in BRCA mutated epithelial ovarian
cancer
Khayal Gasimli1; Morva Tahmasbi Rad1; Monika Raab1; Sven Becker1;
Elisabeth Kurunci-Csacsko1; Klaus Strebhardt1,2; Mourad Sanhaji1
1Universitätsklinikum Frankfurt, Gynäkologie und Geburtshilfe, Frankfurt am
Main, Deutschland
2German Cancer Consortium (DKTK), Partner Site Frankfurt am Main, Frankfurt
am Main, Deutschland
Background: Currently, the treatment of epithelial ovarian cancer (EOC)
remains largely ineective, and recurrent resistance to platinum-based
chemotherapy represents the major challenge in EOC management.
Emerging data report that BRCA-mutated cancers may also resist PARPi.
PLK1 is a crucial regulator of cell cycle progression. Its protein expression
is signicantly elevated in ovarian cancers.
Methods: To explore the role of PLK1 in sensitizing EOC cells, OVSAHO
and KURAMOCHI, and patient derived 3D-spheroids underwent a
mono- or a combination therapy using the PLK1 inhibitor BI6727, the
PARP inhibitor Olaparib, and Carboplatin. e cell survival upon the
treatments was investigated using the 2D clonogenic assay. In addition, the
cell death triggered by the dierent treatment conditions has been inves-
tigated by assessing the enzymatic activation of the eector caspases 3/7
(Caspase 3/7 Glo assay) and using Annexin/AAD staining. Additionally,
the eects of the mono and the combinatorial treatments on the growth of
the BRCA-mutated cell lines-based 3D-spheroids were evaluated by mea-
suring the spheroid volumes aer a dened period post treatment.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts118
Result: Our study shows that PLK1 inhibition with the specic inhibi-
tor BI6727 triggers a robust sensitization of ovarian cancer with BRCA-
mutations and patient derived cancer cells to Olaparib. Furthermore,
the combination of Olaparib and BI6727 signicantly reduced the
survival of ovarian cancer cells in 2D and 3D cell models upon plati-
num-based chemotherapy, initiates mitochondrial apoptosis by inactivat-
ing the anti-apoptotic BCL-2 family proteins, followed by activation of
caspase-dependent eector pathways. We found that that PLK1 inhibition
signicantly strengthens Olaparib-associated cell death in BRCA-mutated
EOC, supporting the translation of this combination, Olaparib/ BI6727,
into a clinical trial.
Conclusion: Our ndings elucidate the critical role of PLK1 in the resis-
tance to PARPi in BRCA-mutated EOC and suggest a new combinatorial
strategy that may improve platinum-based ecacy.
Disclosure Statement: e authors declare no conict of interest.
620
Poor sialic acids moieties on glycosphingolipids conduct
metastatic formation in ovarian cancer
Cecile Cumin1; Arun Everest-Dass2; Yen-Lin Huang1; Charlotte Rossdam3;
Natalie Rimmer1; Ching-Yeu Liang1; Monica Nunez-Lopez1;
Viola Heinzelmann-Schwarz1,4; Falk Buettner3; Francis Jacob1
1University Hospital Basel, Ovarian Cancer Research, Department of
Biomedicine, Basel, Schweiz
2Grith University, Institute for Glycomics, Gold Coast, Australien
3Hannover Medical School, Institute for Clinical Biochemistry, Hannover,
Deutschland
4University Hospital Basel, Hospital for Women, Department of Gynecology and
Gynecological Oncology, Basel, Schweiz
Background: To invade the peritoneal cavity and form metastatic sites,
ovarian cancer cells need to undergo reversible epithelial-to-mesenchy-
mal transition (EMT/MET). Here, depletion of globosides (ΔA4GALT),
a subclass of glycosphingolipids (GSLs) has been aliated with EMT-
associated ovarian cancer spreading [1]. However, the GSL-mediated
mechanism contributing to primary and metastatic formation remains
unclear.
Methods: We rst investigated intra-patient heterogeneity for E-cadherin
and GSLs using tissue microarrays with matched samples and MALDI-
MSI, respectively. Bulk and single cell transcriptomic datasets were
assessed to align GSL-encoding gene with EMT marker expression. us,
the identied ganglioside synthesizing enzyme ST8SIA1 was homozy-
gously knocked out using CRISPR-Cas9, validated by xCGE-LIF, in vitro
and in vivo assays. Associated signaling pathways were dissected by (phos-
pho-) proteomic analysis.
Results & Discussion: E-cadherin was persistently expressed in the
tumor compartment independent of the time of disease and showed co-
expression with globosides while gangliosides were associated to the mes-
enchymal-like stroma. Genetic deletion of ST8SIA1 (ΔST8SIA1) reduced
the expression of mesenchymal (Vimentin) and increased epithelial mark-
ers (E-cadherin, Claudin 1&3). Interestingly, loss of sialic acids on gan-
gliosides reduced the cell capacity migrate (p < 0.05) but increased their
competence to form spheroids in 3D cultures (p < 0.05) and tumor growth
in tumor xenogras. In contrast, loss of globosides in ΔA4GALT cells
demonstrated an invasive behavior. Finally, phosphoproteomics identied
a decrease of phosphorylation of peptides such as MTOR, MAPK1 and
AKT in ΔST8SIA1 which is usually associated with MET while pathways
related to calcium were enriched in ΔA4GALT cells.
Conclusion: We provide the rst evidence that GSLs play an important
role in EMT and MET. ese data suggest that sialic acid -rich GSLs may
be an important driver of EMT-associated pathways.
Reference:
1. Jacob et al. Cancer Res. 2018, 78(11):2952-2965. PMID: 29572228
Disclosure Statement: e authors declare no conict of interest.
629
NK cell-mediated eradication of ovarian cancer cells with a
novel chimeric antigen receptor directed against CD44
Jens Hachenberg1,2; Katharina Zimmermann2; Michael Morgan2;
Peter Hillemanns1; Axel Schambach2; Rüdiger Klapdor1,2
1Medizinische Hochschule Hannover, Klinik für Frauenheilkunde und
Geburtshilfe, Hannover, Deutschland
2Medizinische Hochschule Hannover, Institut für experimentelle Hämatologie,
Hannover, Deutschland
Background: Despite advances in adjuvant therapy, most ovarian cancer
(OC) patients suer from recurrent disease. Ovarian cancer stem cells
(CSC) represent a source of tumor recurrence. CSC are characterized by
high resistance to chemotherapy and enhanced tumorigenicity. Chimeric
antigen receptor (CAR)-based adoptive immunotherapy represents a
promising strategy to reduce the risk for recurrent disease. We evaluated a
third-generation CAR against CD44, an ovarian CSC marker.
Methods: We used OC cell lines A2780, SKOV3, and OVCAR3 as well as
primary OC cells. We generated an anti-CD44 CAR based on a third-gen-
eration CAR design containing CD28 and 4-1BB as co-stimulatory
domains. NK-92 cells were equipped with the novel CAR constructs by
lentiviral transduction. We performed IFNγ release assays to demonstrate
specic activation of engineered NK cells. Live cell impedance analysis
with xCELLigence was used to estimate the anti-tumor activity of NK
cells. NK cells and cisplatin were added to A2780 or primary OC cells
to investigate the feasibility of this combination. Aer treatment, analy-
sis was accomplished using the CellTiter 96® AQueous One Solution Cell
Proliferation Assay.
Result: NK-92 cells equipped with the anti-CD44 CAR (CD44NK)
showed specic cytotoxic activity against CD44-positive OC cells and
primary OC cells. IFNγ secretion assays indicated specic activation of
the engineered cells aer incubation with target cells. Additionally, we
evaluated the treatment combinations of CD44NK cells and cisplatin.
e simultaneous treatment with CD44NK and cisplatin showed higher
anti-tumor activity compared to sequential treatment.
Conclusion: e new anti-CD44 CAR exhibited specic killing in OC
cell lines and primary OC cells. CD44NK cells retained their cytotoxic-
ity during cisplatin incubation. e most potent anti-tumor eect was
achieved by simultaneous treatment with CD44NK cells and cisplatin.
is study will be the basis for further in vivo studies and future clinical
developments.
Disclosure Statement: e authors declare no conict of interest.
640
A functional CRISPR screen to determine PARP inhibitor
sensitivity in ovarian cancer
Ricardo Coelho1; Muriel Disler1,2; Alessandra Tozzi1,2; André Fedier1; Viola
Heinzelmann-Schwarz1,2; Francis Jacob1
1University Hospital Basel, Department of Biomedicine, Ovarian Cancer
Research, Basel, Schweiz
2University Hospital Basel, Gynecological Cancer Center, Hospital for Women,
Basel, Schweiz
Background: Poly (ADP-ribose) polymerase inhibitors (PARPi) have
transformed the therapeutic landscape of high-grade serous ovarian
cancer. Maintenance strategies with PARPi have been assessed in vari-
ous clinical trials and shown improvement in progression-free survival
for carriers of BRCA1/2 mutation1,2. Interestingly, these data also point
towards an extended benet of PARPi for patients with homologous
recombination (HR)- deciency beyond BRCA1/2 alterations. erefore,
there is an urgent need to unveil “true” predictive biomarkers for PARPi
response.
Methods: Design and lentivirus deliver of sgRNAs targeting candidate
genes (n=21) into Cas9+ ovarian cancer cell lines (n=5) together with
Olaparib-PARPi selective pressure. Target genes were selected based on its
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 119
role of cancer “cell tness” and involvement in HR repair pathway identi-
ed by a literature-based search and publicly available data from Cancer
Cell line Encyclopedia.
Results/Discussion: Despite variations in “cell tness, a cell line-inde-
pendent sensitivity to Olaparib was observed for the genomic disruption
of BRCA1/2 in all cell lines tested. In contrast, genes such as ATM, RAD51,
RAD51B, RAD51C, RAD51D, XRCC3 and XRCC2 revealed a cell line-de-
pendent dropout rate suggesting that several HR repair-related genes
depend on additional factors to confer Olaparib sensitivity.
Conclusions: We established a functional CRISPR screen and identied
genes conferring sensitivity to Olaparib shedding light on the importance
of a functional assay to identify “true” predictive biomarkers. Ongoing
work investigates gene dependencies in regards to dierent PARPi and its
translation in patient-derived tissue samples.
References:
1 Gonzalez-Martin, A. et al. Niraparib in Patients with Newly Diagnosed
Advanced Ovarian Cancer. N Engl J Med 381, 2391-2402, doi:10.1056/
NEJMoa1910962 (2019).
2 Moore, K. et al. Maintenance Olaparib in Patients with Newly Diagnosed
Advanced Ovarian Cancer. N Engl J Med 379, 2495-2505, doi:10.1056/
NEJMoa1810858 (2018).
Disclosure Statement: e authors declare no conict of interest.
654
Niraparib ecacy and safety in patients with BRCA-mutated
(BRCAm) ovarian cancer: results from three phase 3 niraparib
trials
Antonio González-Martín1,2; Jacek Grabowski3; Ursula Matulonis4;
Jacob Korach5; Mansoor Mirza6; Kathleen Moore7; Divya Gupta8;
Stanislav Lechpammer8; Bradley J Monk9
1Grupo Español de Investigación en Cáncer de Ovario (GEICO), Madrid, Spanien
2Clínica Universidad de Navarra, Madrid, Spanien
3Campus Virchow Clinic, Charité Comprehensive Cancer Center (CCCC), Charité
Medical University Berlin, Berlin, Deutschland
4Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA
5Sheba Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv,
Israel
6Rigshospitalet, Copenhagen University Hospital, Copenhagen, Dänemark
7Stephenson Cancer Center, University of Oklahoma Health Science Center,
Oklahoma City, USA
8GlaxoSmithKline, Waltham, USA
9Arizona Oncology (US Oncology Network), University of Arizona College of
Medicine, Creighton University School of Medicine, Arizona, USA
Background: Niraparib is approved for the maintenance treatment
of patients (pts) with advanced or recurrent ovarian, fallopian tube, or
primary peritoneal cancer (OC) aer chemotherapy (CT). Here, we
summarize niraparib ecacy and safety in pts with BRCAm OC across
three phase 3 trials: PRIMA/ENGOT-OV26/GOG-3012 (PRIMA;
NCT02655016), ENGOT-OV16/NOVA (NOVA; NCT01847274), and
NORA (NCT03705156).
Methods: Pts enrolled in PRIMA had newly diagnosed advanced OC. All
pts had stage III/IV high-grade serous or endometrioid tumors and had
a complete or partial response to rst-line platinum-based CT. Subgroup
analysis by tumor BRCAm status was prespecied. Pts enrolled in NOVA
and NORA had platinum-sensitive, high-grade serous OC and received
≥2 lines of platinum-based CT. In both studies, subgroup analysis by ger-
mline BRCAm status was prespecied. e primary endpoint in all tri-
als was progression-free survival (PFS) by blinded independent central
review.
Results: e BRCAm populations from each trial are as follows: 223
(148 BRCA1m and 75 BRCA2m) from PRIMA, 203 (128 BRCA1m, 69
BRCA2m, and 13 BRCA1/2m) from NOVA, and 100 (78 BRCA1m,
21 BRCA2m, and 1 BRCA1/2m) from NORA. In PRIMA, median PFS
(mPFS) was 22.1 vs 10.9 mo with niraparib vs placebo (PBO) in BRCAm
pts (hazard ratio [HR] 0.40, 95% CI 0.27–0.62). In gBRCAm pts in NOVA,
mPFS was 21.0 vs 5.5 mo with niraparib vs PBO (HR 0.27, 95% CI
0.17–0.41). In NORA, mPFS was not reached in gBRCAm pts receiving
niraparib and was 5.5 mo with PBO (HR 0.22, 95% CI 0.12–0.39). mPFS
HRs (95% CI) in pts with BRCA1m and BRCA2m in PRIMA were 0.39
(0.23–0.66) and 0.35 (0.15–0.84), respectively. Across the 3 trials, the most
common treatment-emergent adverse events were thrombocytopenia,
anemia, neutropenia, and hypertension.
Conclusion: Patients with BRCAm OC derived a signicant PFS benet
from niraparib maintenance treatment across all 3 trials. No new safety
signals were identied.
© 2021 American Society of Clinical Oncology, Inc. Reused with
permission.
Disclosure Statement: e authors declare the following: Funding: NOVA
(213356)/PRIMA (213359), GSK; NORA, Zai Labs.
662
Validation of epigenetic and genetic alterations of ITIH5 in
cervical scrapes
Lisa-Marie Lipfert1; Nadja Ziller1; Angelique Ziegfeld1; Stefanie Schütze1;
Julia Vorwergk1; Katrin Beer1; Mieczyslaw Romuald Gajda2;
Anita Homann2; Nicolaus Gaßler2; Ingo B. Runnebaum1; Matthias Dürst1;
Claudia Backsch1
1Klinik und Poliklinik für Frauenheilkunde und Fortpanzungsmedizin,
Universitätsklinikum , Jena, Deutschland
2Sektion Pathologie des Instituts für Rechtsmedizin, Universitätsklinikum, Jena,
Deutschland
Purpose: Progression of human papillomavirus-induced premalignant
cervical intraepithelial neoplasia (CIN) to cervical cancer is driven by
epi(genetic) events. Previous studies revealed a progressive down-regula-
tion of the gene ITIH5 in the course of cervical carcinogenesis. Promoter
methylation in conjunction with deletions in the gene region of ITIH5
seem to be contribute to notable ITIH5 downregulation as shown in in
vitro studies using cervical cancer cell lines and cryosections of cervical
lesions. Aim of the current study is to validate (epi)genetic alterations of
ITIH5 in cervical scrapes of CIN of dierent severity.
Methods: In order to investigate the genetic status of ITIH5, cervical
scrapes of patients with histologically conrmed low grade lesions (CIN1)
(n=20) and high grade lesions (CIN2-3) (n=60) are analysed using a
locus-specic probe for ITIH5 and a control probe for centromere 10 for
direct interphase uorescence in situ hybridization. In parallel, ITIH5
promoter methylation is investigated by qualitative and quantitative
methylation specic PCR in the same clinical samples.
Results: Preliminary results for CIN2-3 showed a higher number of cases
with copy number loss of ITIH5 as well as ITIH5 DNA methylation com-
pared to CIN1. Additionally, in some cases of CIN2-3 a loss of centromere
10 was detected. Investigations are still ongoing.
Conclusions: A combined screening of the copy number state of ITIH5
and the methylation pattern may help in the early detection of human
papillomavirus- induced genetic instabilities and genetic modications
and may be useful as novel molecular markers for progression of CIN.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts120
663
Constitutive BRCA1 promoter methylation in early-onset
ovarian cancer
Johanna Schmolling1; Jan Hauke1; Alexander Volk2; Dimo Dietrich3;
Mohamad Kayali1; Sandra Schmidt1; Rita Katharina Schmutzler1;
Eric Hahnen1
1Uniklinik Köln, Zentrum Familiärer Brust- und Eierstockkrebs, Köln, Deutschland
2Universitätsklinikum Hamburg-Eppendorf, Institut für Humangenetik,
Hamburg, Deutschland
3Universitätsklinikum Bonn, Klinik und Poliklinik für Hals-Nasen-Ohren-
Heilkunde, Bonn, Deutschland
Background: e prevalence of germline BRCA1/2 (gBRCA1/2) muta-
tions in patients with early-onset ovarian cancer (OC) is compara-
tively low. Of the patients documented in the German Consortium for
Hereditary Breast and Ovarian Cancer (GC-HBOC) registry, 35/433 OC
patients with an onset ≤35 years carried gBRCA1/2 mutations (8.1%); this
proportion increased to 20.0% (146/729) and 37.4% (752/2012) with a
cut-o of ≤40 or ≤50 years, respectively. Besides non-BRCA1/2 risk genes
which may associate with early onset OC, it was recently suggested that
constitutive BRCA1 promoter hypermethylation, measurable in blood-de-
rived DNA, may be an OC risk factor.
Methods: We analysed a clinical sample of 455 gBRCA1/2 mutation-neg-
ative OC patients with early onset (≤40 years) for germline mutations
in additional established OC risk genes (BRIP1, RAD51C/D, MSH2/6)
and quantied BRCA1 promoter methylation in blood-derived DNA in
423 of these patients and an additional 476 female cancer-free control
individuals.
Result: Pathogenic germline mutations in the additional OC risk genes
were identied in ve of the 455 patients only (1.1%, 1 BRIP1, 1 MSH2,
1 MSH6, 2 RAD51C). e quantitative methylation analysis revealed
BRCA1 promoter hypermethylation (≥5% cut-o) in 26 of the 423 OC
patients examined (6.1%) which was signicantly higher than in controls
(7/476, 1.5%, OR: 4.39, 95%CI: 1.79-11.22, P=0.00025). Results remain
signicant with a ≥2% cut-o (36/423 cases vs. 20/476 controls; OR: 2.12,
P=0.008). e age at onset was 30.5 years (range 14-40) in OC patients
with ≥5% BRCA1 promoter hypermethylation vs. 31.1 years (range 18-40)
without.
Discussion: Our results support the hypothesis that BRCA1 hypermeth-
ylation represents an OC risk factor, though further analyses are required.
Conclusion: Further studies are ongoing in our laboratory to investi-
gate whether BRCA1 hypermethylation in blood correlates with BRCA1
hypermethylation in the corresponding tumour samples.
Disclosure Statement: e authors declare no conict of interest.
674
Ecacy of niraparib by timing of surgery and residual disease:
a post-hoc analysis of patients in the PRIMA/ENGOT-OV26/
GOG-3012 study
Roisin O’cearbhaill1; Jacek Grabowski2; Jose-Alejandro Pérez-Fidalgo3;
Bradley J Monk4; Ignacio Tusquets5; Colleen Mccormick6; Jose Fuentes
Pradera7; Richard. G. Moore8; Christof Vulsteke9,10; Mark Shahin11; Frederic
Forget12; William H. Bradley13; Sakari Hietanen14; David O’malley15; Anne
Dørumn16; Brian M. Slomovitz17; Klaus Baumann18; Frédéric Selle19; Paula
M. Calvert20; Grazia Artioli21; Tally Levy22; Aalok Kumar23; Izabela
Malinowska24; Yong LI24; Divya Gupta24; Antonio González-Martín25
1GOG and the Department of Medicine, Memorial Sloan Kettering Cancer
Center, Weill Cornell Medical College, New York, USA
2Department of Gynecology, Campus Virchow Clinic, Charité Comprehensive
Cancer Center (CCCC), Charité Medical University Berlin, Berlin, Deutschland
3INCLIVA University Hospital of Valencia, CIBERONC, Department of Medical
Oncology, Valencia, Spanien
4University of Arizona College of Medicine, Creighton University School of
Medicine , Arizona Oncology (US Oncology Network), Phoenix, USA
5Hospital del Mar, Medical Oncology Department, Barcelona, Spanien
6GOG and Legacy Medical Group Gynecologic Oncology, Portland, USA
7Hospital de Valme, Servicio de Oncologia, Sevilla, Spanien
8Division of Gynecologic Oncology, Wilmot Cancer Institute, Department of
Obstetrics and Gynecology, University of Rochester, Rochester, USA
9BGOG and the Department of Medical Oncology and Hematology, AZ Maria
Middelares, Ghent, Belgien
10Antwerp University, Center for Oncological Research, Department of Molecular
Imaging, Pathology, Radiotherapy and Oncology, Antwerp, Belgien
11Abington Hospital-Jeerson Health, Sidney Kimmel Cancer Center of Thomas
Jeerson University, Willow Grove, USA
12Libramont Hospital, Department of Medical Oncology, Libramont, Belgien
13GOG and the Department of Obstetrics and Gynecology, Medical College of
Wisconsin, Milwaukee, USA
14Turku University Hospital, Department of Obstetrics and Gynecology, Turku,
Finnland
15James Comprehensive Cancer Center, Ohio State University, Columbus, USA
16The Norwegian Radiumhospital, Oslo University Hospital, Gynecologic
Oncology, Oslo, Norwegen
17Broward Health, Florida International University Wertheim College of
Medicine, USA
18Arbeitsgemeinschaft Gynäkologische Onkologie and the Department of
Gynecology and Obstetrics, Klinikum der Stadt Ludwigshafen, Ludwigshafen,
Deutschland
19GINECO and Groupe Hospitalier Diaconesses-Croix Saint Simon, Paris,
Frankreich
20Cancer Trials Ireland, Dublin, Irland
21ULSS 3 Serenissima, U.O.C. Oncologia ed Ematologia Oncologica, Venice,
Italien
22Sackler School of Medicine, Tel Aviv University, Wolfson Medical Center,
Department of Obstetrics and Gynecology, Holon, Israel
23Fraser Valley Cancer Centre, BC Cancer, Department of Medical Oncology,
Surrey, Kanada
24GlaxoSmithKline, Waltham, USA
25Grupo Español de Investigación en Cáncer de Ovario (GEICO) and Medical
Oncology Department, Clínica Universidad de Navarra, Madrid, Spanien
Background: Niraparib is approved as maintenance treatment for
patients (pts) with newly diagnosed advanced/recurrent ovarian, pri-
mary peritoneal, or fallopian tube cancer (OC) aer response to plati-
num-based chemotherapy (CT). e PRIMA/ENGOT-OV26/GOG-3012
(NCT02655016) study showed that niraparib following rst-line (1L)
treatment improved progression-free survival (PFS) in the overall inten-
tion-to-treat (ITT) population (hazard ratio [HR] 0.62; 95% CI 0.50–0.76).
Methods: is double-blind, placebo (PBO)-controlled, phase 3 trial eval-
uated niraparib in pts with newly diagnosed, advanced, high-grade serous
or endometrioid OC with a complete or partial response to 1L CT. Pts
were considered to be at high risk for disease progression based on their
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 121
clinical characteristics. is post-hoc analysis presents niraparib ecacy
(PFS) by time of surgery and residual disease status, and was not powered
to determine dierences among subgroups.
Result: Data cuto was May 2019. In total, 733 pts were randomized in
PRIMA. Pts who underwent primary debulking surgery (PDS; n=236) or
interval debulking surgery with neoadjuvant CT (IDS, n=481) had simi-
lar ecacy with niraparib maintenance treatment versus PBO in the ITT
population (PFS HRs [95% CI] were 0.67 [0.468–0.964] and 0.57 [0.441–
0.731], respectively). Niraparib treatment reduced risk of progression
by 42% (95% CI 0.391–0.864) in pts who received PDS and had visible
residual disease (VRD, n=183), 35% (95% CI 0.461–0.91) in those with
IDS and no visible residual disease (NVRD, n=304), and 59% (95% CI
0.269–0.620) in those with IDS and VRD (n=149). Ecacy was not evalu-
able for pts with PDS and NVRD due to low sample size (n=37).
Discussion: In this post-hoc analysis, the impact of residual disease aer
PDS or IDS on the ecacy of niraparib was comparable across subgroups.
Pts with IDS and VRD had the highest reduction in the risk of progression.
Conclusion: ese results suggest timing of surgery does not impact
niraparib ecacy.
Previously presented at SGO 2021; reused with permission.
Funding: GSK 213359.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
764
QuantiGene-Molecular Proling Histology assay shows
superior accuracy in cervical dysplasia detection by
multiplexed Human Papillomavirus oncogene and cellular
biomarker expression quantitation
Nicole Schaefer1; Gunther Schauberger2; Anna Sophie Skof1;
Stefanie Klug2; Andreas Kaufmann1
1Clinic for Gynecology, Charité-Universitätsmedizin Berlin, HPV Laboratory,
Berlin, Deutschland
2Department of Sport and Health Sciences, Technical University of Munich,
Epidemiology, München, Deutschland
Background: Cervical dysplasia are caused by HPV and accompanied by
cellular biomarker upregulation. Screening programs switch from cytol-
ogy to HPV testing. While HPV tests have a higher sensitivity (95% vs.
50%), the specicity is low (<40%). Expression quantitation of cellular
progression-associated biomarkers may enhance specicity and diag-
nosis of dysplastic stages. QuantiGene-Molecular Proling Histology
(QG-MPH) assay enables ecient multiplexed HPV oncogene and bio-
marker mRNA detection and quantitation.
Methods: e QG-MPH assay was designed, individually quantifying
E7 oncogene mRNA of 18 high-risk HPVs, cellular housekeeping genes,
and 10 established biomarkers in a multiplexed format. On a referral
population logistic regression and ROC-analyses were performed and
risk scores with related cut-o values were calculated for disease stages
CIN2+, CIN3+, and CxCa. A nested sample set (550 patients) of a popula-
tion-based cohort (MARZY study, Mainz, Germany) was reanalysed. e
risk score results were compared to standard of care screening methods
(PAP, LBC, HC2, GP5+/6+-PCR) and four dierent co-testing variants
(PAP+HC2, PAP+PCR, LBC+HC2, LBC+PCR). Histological endpoints
CIN2+ and CIN3+ were evaluated.
Result: 61 women (all peculiar plus 5% randomly selected healthy con-
trols) had a histology endpoint. Nine CIN2+ and six CIN3+ were histo-
logically conrmed. Sensitivity and specicity for detection by QG-MPH
risk scores was 67% and 83% for CIN2+, and 83% and 82% for CIN3+,
respectively. Cytology was less sensitive (PAP: 33%; LBC: 33%) and simi-
larly specic (PAP: 79%; LBC: 89%) for the detection of CIN3+. e HPV
tests and the four co-testing strategies had similar sensitivities (83%) but
lower specicities (range 26-67%).
Discussion/Conclusion: Due to equal sensitivity but signicantly higher
specicity compared to all HPV- and co-testing approaches to detect
CIN3+, the QG-MPH assay presents a potentially superior method for
cervical cancer screening. ese data warrant further assay evaluation in
larger prospective screening cohorts.
Disclosure Statement: e authors declare the following: Patent, Honorae,
Beratergremien
776
Monocentric evaluation of radio(chemo)therapy [R(C)T]
forvulval squamous cell carcinoma (VSCC)
Jacqueline Possiel; Katja Döring Laura Anna Fischer;
Markus Anton Schirmer; Manuel Guhlich; Andrea Hille;
Stefan Rieken; Leif Hendrik Dröge; Sandra Donath; Martin Leu
Universitätsmedizin Göttingen, Klinik für Strahlentherapie und Radioonkologie,
Göttingen, Deutschland
Background: Radical vulvectomy is the standard of care for VSCC.
Denitive R(C)T plays a crucial role as alternative treatment in patients
(pat) with inoperable VSCC. To date, hardly any prospective study has
evaluated the outcome of those pat.
Methods: We retrospectively analyzed 57 pat ≥18 years without distant
metastasis that received radiotherapy at our hospital. Patient and tumor
characteristics, comorbidities as well as acute and late toxicities were
analyzed. e primary endpoints were 5-year overall (OS) and progres-
sion-free survival (PFS), locoregional (LRC) and distant (DC) control.
As statistical methods we used univariable cox-regression and log-rank
statistics.
Results: Median pat age was 74 years (28.0-90.0 years). Median follow-up
was 18 months (2.0-187.0). 36 patients underwent resection of vulval car-
cinoma followed by postoperative R(C)T. 21 pat received denitive R(C)T.
23/57 pat. were treated with concomitant chemotherapy. IMRT was used
in 18/57 pat. 5-year OS was 60.6%, PFS 46.5%, LRC 55.9% and DC 95.0%.
Normofractionated external beam radiotherapy was administered at a
median total dose of 50.4 Gy (36.0-76.4 Gy). III° side eects were observed
in 15/57, mostly skin reactions (n=15). Patients with multimodal therapy
(surgery + R(C)T) had a signicant better OS (HR 0.19, CI 0.07-0.50,
p<0.01), PFS (HR 0.29, 95% CI 0.13-0.63, p<0.01) and LRC (HR 0.21,
95% CI 0.07-0.61, p<0.01). Additionally, patients with acute toxicities ≥
III° presented a worse OS (HR 3.15, 95% CI 1.24-8.01, p=0.02).
Discussion: is retrospective study shows that R(C)T is generally well
tolerated in pat treated for VSCC and might be considered for pat not suit-
able for surgery, although OS, PFS and LRC are worse. erefore, patient
selection should be evaluated by experienced radiation oncologists and
surgeons based on the patient´s general condition, tumor category and
comorbidities.
Conclusion: R(C)T for the treatment of VSCC is a safe therapy option
with acceptable toxicity.
Disclosure Statement: e authors declare no conict of interest.
828
Combined expression of the progesterone receptor A/RIP140
is a negative independent prognosticator for cervical cancer
Fabian Garrido1; Mathis Wild1; Udo Jeschke1; Christian Dannecker1;
Franziska Dobler1; Bernd Kost2; Sven Mahner2; Helene Heidegger2;
Doris Mayr3; Vincent Cavailles4; Aurelia Vattai2
1University Hospital Augsburg, Department of Obstetrics and Gynecology,
Augsburg, Deutschland
2LMU Munich, University Hospital, Department of Obstetrics and Gynecology,
Munich, Deutschland
3LMU Munich, Department of Pathology, Munich, Deutschland
4Université Montpellier, Institut de Recherche en Cancérologie de Montpellier
(IRCM), INSERM U1194 , Montpellier, Frankreich
Purpose: e role of the progesterone receptor A (PR-A) for cervical
cancer outcome is ambivalent. In mouse models it seems to play a rather
protective role for cancer development. In many other tumor types, PR-A
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts122
expression corresponds to favorable outcome. RIP140 on the other hand,
was already identied as a negative prognostic factor for survival of cer-
vical cancer patients. e aim of this study was to assess the prognostic
value of PR-A in cervical cancer tissue samples and to correlate the results
with clinicopathological parameters.
Methods: In 250 cervical cancer patients, the expression of PR-A was
evaluated by immunohistochemistry. Prognosis determining aspects were
calculated by uni- and multivariate analysis.
Results: Correlation analysis revealed a trend association with RIP140,
HPV virus protein E6, a negative correlation with p16 and a positive
correlation with EP3. PR-A expression was positively correlated with
International Federation of Gynecology and Obstetrics (FIGO) classi-
cation and PR-A was signicantly higher expressed in adeno carcinomas
compared to squamous epithelial carcinoma subtypes. Univariate sur-
vival analyses revealed PR-A as a negative prognosticator for survival.
Multivariate analyses showed that the combined expression of both PR-A
and RIP140 is an independent marker for survival of cervical cancer
patients.
Conclusion: erefore PR-A has to be considered as a negative factor for
cervical cancer survival.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
1015
Preoperative conization of early cervical carcinoma associated
with improved progression free survival, a retrospective
single center analysis
Laura Delebinski1; Hermann Hertel1; Peter Hillemanns1; Rüdiger Klapdor1
1Medizinische Hochschule Hannover, Klinik für Frauenheilkunde und
Geburtshilfe, Hannover, Deutschland
Background: e purpose of this study was to examine the association of
patient characteristics and surgical interventions with the progression free
survival and overall survival in patients with cervical carcinoma.
Methods: In total 276 patients with cervical carcinoma through FIGO
IB1 were included in this singlecenter study. In this retrospective analysis,
multivariate cox regression was performed by adjusting for age, lymph
node status, tumor diameter, grading, preoperative conization, adjuvant
therapy and surgical approach (abdominal, laparoscopic).
Result: For 52,5% of the patients the minimally invasive approach and for
44,9% the open abdominal approach was chosen, respectively. e sur-
gical approach was neither a predictive marker for overall survival (OR
1,220; 95% KI: 0,460 – 3,236; p=0,689) nor for progression free survival
(OR 1,295; 95% KI: 0,548 – 3,06; p=0,556) in our study. However, a preop-
erative conization was the only variable strongly associated with improved
survival (OR 4,022; 95% KI: 1,243 – 13,012; p=0,020).
Discussion: In 114 patients with macroscopically complete tumor resec-
tion by conization 8 recurrences occurred. is could be a surrogate for
the prognostic role of tumor cell contamination during laparoscopic hys-
terectomy in patients with macroscopic tumor.
Conclusion: Patients with preoperative conization represent a low risk
collective that might still prot from laparoscopic hysterectomy. Further
prospective, randomized studies on minimally invasive surgery for cervi-
cal cancer must include techniques to prevent intraoperative tumor cell
contamination.
Disclosure Statement: e authors declare no conict of interest.
1050
The Comparative Clinical Eectiveness of Dostarlimab
(dostar) Versus Doxorubicin (dox) in the Treatment (tx) of
Advanced/Recurrent Endometrial Cancer (A/R EC)
Theresa Link1; Cara Matthews2; Domenica Lorusso3,4; Robert L. Coleman5;
Daniel Parks6; Susan Boklage6; Jamie Garside7
1Department of Gynecology and Obstetrics, Technische Universität Dresden,
Dresden, Deutschland
2Brown University, Providence, USA
3Fondazione Policlinico Gemelli of Rome, Rom, Italien
4Department of Gynecologic Oncology, Catholic University of Sacred Heart,
Rom, Italien
5Texas Oncology, US Oncology Research, Dallas, USA
6GlaxoSmithKline, Upper Providence, Collegeville, USA
7GlaxoSmithKline, London, Vereinigtes Königreich
Background: Dostar is approved for patients (pts) with A/R mismatch
repair decient/microsatellite instability high (dMMR/MSI-H) EC. Its
ecacy was evaluated in the single arm GARNET trial (NCT02715284).
Systematic literature review identied the dox control arm of the ZoptEC
trial (NCT01767155) for indirect tx comparison vs GARNET using
pt-level data.
Methods: GARNET Cohort A1 (dMMR/MSI-H A/R EC) and ZoptEC
dox (A/R EC) pts were matched by eligibility criteria. A sensitivity anal-
ysis included all pts who received study drug in both arms. For overall
survival (OS) in months, a Cox proportional hazards model with inverse
probability of tx weighting (IPTW) was used. Kaplan–Meier analysis was
used for progression-free survival (PFS), duration of response (DoR) and
time to deterioration (TTD) in quality of life (QoL), in months. Overall
response rate (ORR) and safety were summarized descriptively. 95% con-
dence intervals (CIs) were estimated with the Clopper–Pearson method.
Result: Median (m) OS (95% CI) was longer for dostar (n=92) vs dox
(n=233) (NR [18.0–NR] vs 11.2 [10.0–13.1]; hazard ratio [HR] 0.41
[95% CI 0.28–0.61; p<0.0001]). Sensitivity analysis (dostar n=129; dox
n=249) gave similar HR (0.40; 95% CI 0.28–0.58). mPFS (95% CI) was
8.1 (3.2–NR) for dostar vs 4.9 (4.1–6.6) for dox. ORR (95% CI) was 43.5%
(33.2–54.2) for dostar vs 13.7% (9.6–18.8) for dox; mDoR was NR vs 8.4,
respectively. mTTD in QoL (95% CI) was 7.1 (2.8–NR) for dostar (n=62)
and 4.5 (4.1–5.4) for dox (n=188). % of pts with adverse events (AEs) lead-
ing to tx discontinuation (12% vs 15%) and serious AEs (34% vs 30%) were
similar. Grade ≥3 AEs were lower for dostarlimab vs dox (48% vs78%).
Discussion: -
Conclusion: Improved OS was observed with dostar in pts with dMMR/
MSI-H A/R EC vs dox in A/R EC. Safety proles were consistent with
prior studies. is suggests dostar has a favorable benet:risk ratio in
thesepts.
Indication of source: GSK 215333. Data under license from Aeterna Zentaris.
Previously presented at SGO 2022; Phoenix, AZ (#216); presented on behalf of
original authors with permission.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 123
1055
Antitumor activity and safety of dostarlimab therapy in
patients (pts) with endometrial cancer (EC) by age subgroups:
a post-hoc analysis from the GARNET trial
Lars Hanker1; Ana Oaknin2; Lucy Gilbert3; Anna Tinker4; Renaud Sabatier5;
Jubilee Brown6; Cara Matthews7; Valentina Boni8; Vanessa Samouelian9;
David O’malley10; Andrea Jewell11; Susana Banerjee12; Grace Antony13;
Jennifer Veneris14; Bhavana Pothuri15
1Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck, Deutschland
2Hospital Universitari Vall dHebron, Vall dHebron Institute of Oncology (VHIO),
Barcelona, Spanien
3Division of Gynecologic Oncology, McGill University Health Centre, Montreal,
Quebec, Kanada
4BC CancerVancouver, Vancouver, British Columbia, Kanada
5Department of Medical Oncology, Institute Paoli-Calmettes, Marseille,
Frankreich
6Division of Gynecologic Oncology, Levine Cancer Institute, Atrium Health,
Charlotte, NC, USA
7Brown University, Providence, RI, USA
8START Madrid CIOCC (Centro Integral Oncológico Clara Campal), Hospital
Universitario HM Sanchinarro, Madrid, Spanien
9Gynecologic Oncology Service, Department of Obstetrics and Gynecology,
Centre Hospitalier de lUniversité de Montréal, Montreal, Quebec, Kanada
10The Ohio State University College of Medicine, Columbus, OH, USA
11University of Kansas Medical Center, Kansas City, KS, USA
12The Royal Marsden NHS Foundation Trust and Institute of Cancer Research,
London, Vereinigtes Königreich
13GlaxoSmithKline, London, Vereinigtes Königreich
14GlaxoSmithKline, Waltham, MA, USA
15Gynecologic Oncology Group (GOG) and Department of Obstetrics/
Gynecology, Perlmutter Cancer Center, NYU Langone Health, New York, NY, USA
Background: Median age of EC diagnosis is 62 y, yet most EC deaths
occur in pts >65 y (median 70 y). Unmet need in older pts is not addressed
by current standard of care. Dostarlimab is an anti-programmed death
receptor 1 (PD-1) antibody. We report a post-hoc analysis of dostarlimab
antitumor activity and safety by age in pts with dMMR/microsatellite
instability high (MSI-H) EC and MMR procient (MMRp)/MS stable
(MSS) EC.
Methods: GARNET (NCT02715284) is a Phase I, single-arm study of
dostarlimab in pts with advanced/recurrent (A/R) solid tumors. Pts with
dMMR/MSI-H EC were enrolled in Cohort A1 and pts with MMRp/MSS
EC in Cohort A2. Pts were stratied: <65 y, ≥65 to <75 y, or ≥75 y at base-
line. Antitumor activity and safety were assessed. Data cut was March 1,
2020.
Result: In Cohort A1 (n=129), 51.2% of pts were <65 y, 39.5% were ≥65
to <75 y, and 9.3% were ≥75 y. In Cohort A2 (n=161), 43.5% were <65 y,
44.7% were ≥65 to <75 y, and 11.8% were ≥75 y. In the ecacy-evaluable
population (measurable disease at baseline; ≥24 w follow up), objective
response rates (ORRs) (95% condence interval [CI]) per RECIST v1.1
assessed by BICR were similar across age groups for pts with dMMR/
MSI-H EC (<65 y: 45.3% [31.6–59.6] vs ≥65 to <75 y: 43.9% [28.5–60.3] vs
≥75 y: 45.5% [16.7–76.6]) and for pts with MMRp/MSS EC (<65 y: 9.1%
[3.4–18.7] vs ≥65 to <75 y: 16.9% [9.0–27.7] vs ≥75 y: 21.1% [6.1–45.6]).
ere were few Grade ≥3 treatment-related adverse events (TRAEs) (for
pts with dMMR/MSI-H EC [n=129]: 13.6% vs 13.7% vs 8.3%, respec-
tively) and for MMRp/MSS EC [n=161]: 22.9% vs 19.4% vs 5.3%, respec-
tively); observed TRAEs were similar between groups.
Conclusion: Dostarlimab antitumor activity and safety for pts with
dMMR/MSI-H EC and MMRp/MSS EC were comparable across age
groups, with low Grade ≥3 TRAE incidence. Older pts with A/R dMMR/
MSI-H EC experienced broadly similar treatment benets as younger pts.
Indication of source: GSK 213346. Previously presented at SGO, Phoenix, AZ;
Mar 18–21 2022 (abstract #210) and presented at DKK 2022 on behalf of original
authors with their permission.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts124
Head and Neck Cancer
Best-of-Abstract-Vortrag
63
HANNA: Eectiveness and quality-of-life data from a
real-world study of patients (pts) with recurrent and/or
metastatic squamous cell carcinoma of the head and neck
(R/M SCCHN) treated with nivolumab (NIVO) in Germany
Harald Müller-Huesmann1; Eyck von der Heyde2; Dennis Hahn3;
Christine Langer4; Boris Kubuschok5; Ulrike Bockmühl6; Gunter Klautke7;
Paul-Stefan Mauz8; Bernd Reuter9; Dirk Beutner10; Jens Büntzel11;
Jens von der Grün12; Chia-Jung Busch13; Bálint Tamaskovics14;
Jorge Riera-Knorrenschild15; Kerstin Gutsche16; Manfred Welslau17;
Thomas Gauler18; Daniela Waldenberger19; Andreas Dietz20
1Brüderkrankenhaus St. Josef Paderborn, Paderborn, Deutschland
2Onkologische Praxis am Raschplatz, Hannover, Deutschland
3Klinikum der Landeshauptstadt Stuttgart, Stuttgart, Deutschland
4Universitätsklinikum Gießen und Marburg, Gießen, Deutschland
5Universitätsklinikum Augsburg, Augsburg, Deutschland
6Klinikum Kassel, Kassel, Deutschland
7Klinikum Chemnitz gGmbH, Chemnitz, Deutschland
8Universitätsklinikum Tübingen, Klinik für Hals-, Nasen- und Ohrenheilkunde,
Tübingen, Deutschland
9SRH Zentralklinikum Suhl GmbH, Suhl, Deutschland
10Universitätsmedizin Göttingen, Klinik und Poliklinik für Hals-Nasen-
Ohrenheilkunde, Göttingen, Deutschland
11Südharz Klinikum Nordhausen gGmbH, Nordhausen, Deutschland
12Universitätsklinikum Frankfurt, Klinik für Strahlentherapie, Frankfurt,
Deutschland
13Universitätsmedizin Greifswald, Klinik und Poliklinik für Hals-, Nasen- und
Ohrenheilkunde, Greifswald, Deutschland
14Universitätsklinikum Düsseldorf, Klinik für Strahlentherapie und
Radioonkologie, Düsseldorf, Deutschland
15Philipps-Universität Marburg, Marburg, Deutschland
16Carl-Thiem-Klinikum Cottbus gGmbH, Cottbus, Deutschland
17Klinikum Aschaenburg, Hämato-Onkologische Schwerpunktpraxis,
Aschaenburg, Deutschland
18Universitätsklinikum Essen, Klinik für Strahlentherapie, Essen, Deutschland
19Bristol Myers Squibb, München, Deutschland
20Universitätsklinikum Leipzig, Klinik und Poliklinik für Hals-, Nasen-,
Ohrenheilkunde, Leipzig, Deutschland
Background: HANNA (NCT03114163) is a prospective, multicenter
study in Germany that collects real-world data from pts with R/M
SCCHN treated with NIVO aer platinum (pt)-based therapy. Overall,
487 adult pts with R/M SCCHN were enrolled and treated according to
the NIVO label.
Methods: is interim analysis represents data from 477 analyzable pts
enrolled until Jul 2021. e primary study objective is overall survival
(OS, estimated using the Kaplan-Meier method). Secondary study objec-
tives include duration of treatment (DOT), safety, patient-reported out-
comes (PROs) and quality of life (QoL) measured with FACT-H&N, and
EQ-5D questionnaires. All data were analyzed in a descriptive manner.
Result: Median follow-up was 32.9 mo. Median age was 64 (range 30–86)
years. Most pts were men (81.1%), and most pts (74.2%) had a history
of smoking. ECOG PS was 0/1/2/3 in 14.0/44.9/24.7/5.9% of pts, respec-
tively. e locations of the primary tumor were oropharynx, 37.7%; oral
cavity, 22.2%; hypopharynx, 19.1%; larynx, 14.7%; and others, 6.3%.
47.2% of pts received NIVO as rst-line (1L) therapy for R/M SCCHN
aer pt-based therapy, 43.8% in 2L, and 9.0% in third/later lines (3+L).
Median OS (mOS) was 10.9 mo. Former/current smoking did not impair
mOS (10.9 mo for current/former smokers vs 10.4 mo for non-smokers,
P=0.8932). mOS was 20.2, 11.0, and 6.1 mo for pts with ECOG PS 0,1, and
2+, respectively. e overall median DOT (mDOT) was 5.4 mo. mDOT
was 5.7 mo for 1L, and 5.3 mo for 2L and 4,6 mo for 3L. For pts with
ECOG PS 0, 1, 2, and 3, mDOT was 8.8, 5.3, 3.3, and 1.9 mo, respectively.
Grade 3/4 treatment-related or immune-related adverse events were
observed in 11,9% of all pts. QoL measured with FACT-H&N remained
stable until mo 24 overall and in all subscale scores. PROs measured with
EQ-5D reected similar outcomes.
Discussion & Conclusion: Real-world data from HANNA show that
NIVO is eective in a broad patient population. e treatment is well tol-
erated and the PRO/QoL remained stable under therapy.1
Source:
1. Previously presented at ESMO 2021, FPN 924P, H. Müller-Huesmann et al.
Reused with permission.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
566
Eag1 Potassium Channel in Oral Squamous Cell Carcinoma – a
proof of principle study
Susanne Wolfer1; Luis Pardo2; Philipp Kaumann1; Boris Schminke1;
Tobias Bürger3; Henning Schliephake1
1Universitätsmedizin, MKG, Göttingen, Deutschland
2Max-Planck-Institut für Experimentelle Medizin, Göttingen, Deutschland
3Universitätsmedizin, Pathologie, Göttingen, Deutschland
Background: Eag1 was among the rst voltage-gated potassium-channels
associated with oncogenesis and tumor development (1). Its expression
prole makes it an interesting new target for tumor therapy (2). Eag1 was
found in many types of tumors, but there were only few studies for head
and neck carcinomas and especially for oral squamous cell carcinoma
(OSCC). is study aimed to screen for Eag1 in OSCC and to correlate its
expression with clinical parameters.
Methods: In this study, OSCC tissue samples were investigated by immu-
nouorescence. Patient-matched normal oral mucosa was used as control.
e expression results were compared to the clinical data. Descriptive sta-
tistics were performed and disease-free-survival was calculated using the
Kaplan-Meier method.
Result: All controls were Eag1 negative. 33 of 46 tumor samples (71.7%)
were positive for Eag1; 14 of them (30.4%) strongly positive. ere was
no correlation to T- or N-stage but bad prognostic factors were more fre-
quent in with Eag1 positive cases (p=0.0017), which showed more recur-
rence (p=0.0059). Two-thirds (76.9%; 10/13) Eag1-negative tumors had
no recurrence event so far. e disease-free-survival was signicantly
shorter in the 14 Eag1 strong positive tumors (p=0.0382). e overall-sur-
vival is also clearly reduced in the strongly positive cases (p=0.0232).
Discussion: A relationship between Eag1 and advanced stages und poorly
dierentiated carcinomas was already known, for larynx and pharynx
(3). We observe similar association on OSCC, but this study is the rst
one to show a signicant association between Eag1 expression and tumor
recurrence.
Conclusion: OSCC shows Eag1 expression that appears to correlate with
prognosis. Investigations with larger sample sizes are necessary to further
conrm these results and clarify the prognostic inuence.
References:
1 Comes N et al. (2015) Biochim Biophys Acta 1848 (2015) 2477–2492
2 Hemmerlein B et al. (2006) Mol Cancer 2006, 5:41
3 Menéndez ST et al. (2012) J Mol Med 2012 90:1173–1184.
Disclosure Statement: e authors declare no conict of interest.
Downloaded from http://karger.com/ort/article-pdf/45/Suppl. 3/6/4143722/000521004.pdf by guest on 05 March 2024
Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 125
Poster
74
125 years of radiotherapy: Could organ sparing radiotherapy
for larynx cancer have prevented World War I?
Thomas Brunner1; Herbert Wördeho1; Ahmed Gawish1; Uwe Busch2
1Universtiätsmedizin Magdeburg, Klinik für Strahlentherapie, Magdeburg,
Deutschland
2German Roentgen Museum, Remscheid, Deutschland
Background: Shortly aer the discovery of x-rays in 1895 curative
organ-sparing radiotherapy (RT) of larynx cancer (LXC) was introduced.
e death of the German Emperor Frederick III (FIII) from untreated
LXC resulted in William II (WII) as his successor on the throne who his-
torically is regarded to be responsible to have led Europe into World War
I (WWI).
Methods: Analysis of historical sources to recapitulate the development
of curative RT for LXC and descriptions of FIII’s LXC and of his treat-
ment were put into political context with a special focus on the escalation
towards WWI, and the role of Emperor WII who succeeded to the crown.
Pertinent historical illustrations of technical developments of RT were
summarized in a video.
Result: e rst reported treatment of head and neck cancer with RT
dates back to February 3, 1896 by Voigt in Hamburg, and Dobson in
London specically described treatment of the larynx in 1901. Both, tele-
therapy and brachytherapy techniques, were developed and rened in
the 20s by Regaud in Paris. FIIIs glottic LXC measured 2 x 4 mm at its
rst description. Queen Victorias son-in-law was treated by German and
English physicians but denite pathological diagnosis was delayed by a
year resulting in cT4 cN1 disease incompatible with cure, and leading to
his death on 15 June 1888. is was eight years before the rst RT of a head
and neck tumour. Nevertheless, FIII could have been cured by voice pre-
serving RT had it been introduced a few years earlier. e hopes were high
that FIII would lead Germany towards a more liberal course reected in
the thoughts of Nietzsche who saw the early death of FIII as a crucial and
decisive tragedy for Germany. FIII was succeeded by WII who led a more
militaristic and expansionistic political regime which probably aected all
of Europe.
Discussion: RT of LXC started strinkingly early aer the discovery of
x-rays and radioactivity shortly aer FIII’s death from a potentially cur-
able LXC.
Conclusion: Organ sparing RT for LXC is a prime example of compatibil-
ity of curative therapy with quality of life.
Disclosure Statement: e authors declare no conict of interest.
111
Radiotherapy or chemoradiation for head and neck tumors - a
cohort of younger patients
Christoph Süß1; Elena Nickel1; Tobias Ettl2; Felix Steger1; Katja Evert3;
OliverKölbl1; Matthias Hautmann1
1Klinik und Poliklinik für Strahlentherapie, Universitätsklinikum Regensburg,
Regensburg, Deutschland
2Klinik und Poliklinik für Mund-, Kiefer- und Gesichtschirurgie,
Universitätsklinikum Regensburg, Regensburg, Deutschland
3Institut für Pathologie, Universitätsklinikum Regensburg, Regensburg,
Deutschland
Background: Radiotherapy and chemoradiation (R(C)T) are well-estab-
lished treatments of locally advanced head and neck carcinoma (HNC).
However, few data exist regarding collectives with patients younger than
40 years. e aim of the present study was to collect and evaluate clinical
parameters, feasibility and outcomes of RCT in a cohort of young patients
with HNC.
Methods: From 2002 to 2019, 78 patients aged 40 years or younger were
included. e collective of 21 women and 57 men had a median age of
38 years at diagnosis, 50 patients suered from HNC UICC stage IVa. 31
patients underwent denitive R(C)T. 47 received resection followed by
adjuvant R(C)T. Simultaneous RCT was performed in 53 patients. Median
follow-up was 21 months (mo) (IQR 10 - 62).
Result: RT was performed as planned in 69% of cases. Interruption of RT
for two or more days occurred in 14 (31%) of 78 patients. In 5 patients,
therapy was discontinued prematurely for various reasons. Of 53 RCT-
treated patients, 32 (60.4%) received a dose > 75% of the initially pre-
scribed chemotherapy. Any acute toxicity ≥ CTC grade III occurred in
32.1% of patients. Twelve weeks aer completion of R(C)T, 57 patients
(73.1%) were free of cancer, and 5 (6.4%) were in partial remission. Overall
survival (OS) was 84% aer 12 mo, 65% aer 24 mo, and 57% aer 60 mo.
Progression-free survival (PFS) of treated patients was 90% aer 12 mo,
79% aer 24 mo and 68% aer 60 mo.
e risk of relapse was signicantly associated with non-HPV-induced
tumors and non-in-sano resection.
Discussion: Regarding side eects and the still improvable prognosis,
currently discussed de-escalation strategies should be evaluated carefully,
especially due to the young age. For patients with high risk for relapse also
an escalation of therapy might be discussed.
Conclusion: Compared to patient cohorts without age selection, young
patients have a better OS and PFS aer 5 years. A multimodal therapy
concept should be aimed at in a collective of younger patients.
Disclosure Statement: e authors declare no conict of interest.
Indication of source:
1 https://doi.org/10.1007/s00066-020-01620-0
131
Methylation and expression signatures of surgical margins in
comparison to tumor and healthy tissue
Tsima Abou Kors1; Jasmin Ezić1,2; Ole Ammerpohl3; Julian Benckendor4;
Thomas F.E. Barth4; Martin Bens5; Jaya Thomas6; Johann M. Kraus7;
Johannes Doescher1; Adrian von Witzleben1; Marie-Nicole Theodoraki1;
Cornelia Brunner1; Jens Greve1; Patrick Schuler1; Thomas K. Homann1;
Christian Ottensmeier6,8; Hans A. Kestler7; Simon Laban1
1Ulm University Medical Center, Department of Otorhinolaryngology and Head
& Neck Surgery, Ulm, Deutschland
2SVA System Vertrieb Alexander GmbH, Wiesbaden, Deutschland
3Ulm University and Ulm University Medical Center, Institute for Human
Genetics, Ulm, Deutschland
4Ulm University Medical Center, Institute of Pathology, Ulm, Deutschland
5Fritz Lipmann Institute, Leibniz Institute on Aging, Jena, Deutschland
6University of Southampton - Faculty of Medicine, Cancer Sciences Unit,
Southampton, Vereinigtes Königreich
7Ulm University and Ulm University Medical Center, Institute of Medical Systems
Biology, Ulm, Deutschland
8University of Liverpool - Faculty of Medicine, Institute of Systems, Molecular
and Integrative Biology - Liverpool Head and Neck Center, Liverpool, Vereinigtes
Königreich
Background: Human papillomavirus (HPV) positive and HPV-negative
oropharyngeal squamous cell carcinoma (OPSCC) (HPV-) dier prog-
nostically and on a molecular level. Traditionally, surgical margins
are assessed patho-histologically, primarily utilizing light-microscopy.
Molecular changes in the tumor bed may predate microscopically detect-
able changes and could result in locoregional recurrence. We aimed to
compare DNA methylation and RNA expression in the primary tumor,
the tumor-free resection margin, and healthy mucosa obtained from
OPSCC patients.
Methods: Aer informed consent, snap-frozen tissue samples of the
tumor, resection margin, and healthy mucosa from 29 OPSCC patients
were obtained intraoperatively. Total RNA and DNA were extracted using
AllPrep DNA/RNA Mini Kit (Qiagen, Germany). DNA methylation
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts126
proling was performed using Innium Methylation EPIC 850K, and
RNA sequencing was performed using Illumina HiSeq2500 (16 tumors)
and Illumina NovaSeq 6000 (rest). Data analysis was performed in R
(4.0.2).
Result: All margin samples were taken from clear resection margin tissue
(R0) with a mean distance of 9mm to the tumor. Exploratory and unsu-
pervised hierarchical clustering analysis conrmed an aggregation based
on tissue type irrespective of HPV status. Signicant dierences in DNA
methylation and gene expression between OPSCC tumor, resection mar-
gin, and healthy mucosa samples were detected.
Discussion: Resection margin data displayed distinct signatures converg-
ing minimally with tumor while intersecting heavily with healthy tissue
signatures.
Conclusion: is project continues establishing methylation and expres-
sion signatures for OPSCC tumor, margin, and healthy mucosa using
Nanopore sequencing.
Disclosure Statement:
Simon Laban: Advisory Boards: Merck Sharp & Dohme (MSD), Bristol Myers
Squibb (BMS), Astra Zeneca (AZ), Sano Genzyme. Honoraria: MSD, BMS,
Merck Serono.
143
Impact of standard therapy on immune checkpoint regulation
in 2D and 3D HNSCC models
Annette Aolter1; Kai Liebel1; Elena Seiz1; Alexya Azhakesan1;
Anne Lammert1; Sonja Ludwig1; Karen Bieback2; Johann Kern1;
Nicole Rotter1
1Klinik für Hals-Nasen-Ohrenheilkunde, Kopf- und Halschirurgie,
Universitätsmedizin Mannheim, Mannheim, Deutschland
2Institut für Transfusionsmedizin und Immunologie, Universitätsmedizin
Mannheim, DRK-Blutspendedienst Baden-WürttembergHessen
gemeinnützige GmbH, Mannheim, Deutschland
Background: e inhibition of immunoregulatory checkpoints such as
the PD-1 / PD-L1 axis is one of the most important immunotherapeutic
strategies for head and neck squamous cell carcinomas (HNSCC). Despite
encouraging results of clinical trials, immunotherapeutic approaches fre-
quently fail to control the tumor disease in patients. Clinical trials evaluat-
ing the combination of immune checkpoint inhibitors (ICI) with already
established therapies are ongoing, but the inuence of these conventional
treatments on immune checkpoint regulation remains elusive.
Methods: Irradiation (IR) alone and in combination with cisplatin or
cetuximab was applied to a HNSCC 2D cell culture model. IR was adapted
to fractionated clinical application schemes. e impact of these standard
treatment pillars on the expression of PD-L1 and signaling pathways
involved in resistance development were assessed by Western Blot, CFA,
and IHC. Results were validated in an ex vivo 3D HNSCC tissue culture
model additionally treated with ICI to consider the therapeutic response
of the tumor microenvironment, particularly immune cells.
Result: A profound induction of PD-L1 by cisplatin was observed in vitro.
Combining IR with cisplatin exerted even stronger eects. Compared to
single IR dosages, the expression of resistance-mediating MAP-Kinase
phospho-ERK1/2 was upregulated aer fractionated IR. Heterogeneity in
PD-L1 expression and ERK phosphorylation was also reected in the ex
vivo model.
Discussion: We provide experimental evidence for an impact of stan-
dard radiochemotherapy on PD-L1 expression in HNSCC. Adaptation of
MAPK to a fractionated IR scheme could indicate a resistance mechanism
to prolonged radiotherapy. e ex vivo culture technology might oer a
promising tool for individualized drug ecacy testing.
Conclusion: Our ndings suggest a complex and probably context-de-
pendent PD-L1 regulation upon application of radiochemotherapy and
further experimental and (pre-)clinical analyses will be essential to
unravel underlying molecular principles.
Disclosure Statement: e authors declare no conict of interest.
146
Volume reduction of salivary glands under Radio(chemo)
therapy (R(C)T) for head and neck tumors
Julia Dressler1; Matthias Hautmann1; Felix Steger1; Manuel März1;
Christian Gröger1; Oliver Kölbl1; Christoph Süß1
1Klinik und Poliklinik für Strahlentherapie, Universitätsklinikum Regensburg,
Regensburg, Deutschland
Background: RT and RCT are important treatment options for head and
neck carcinoma (HNC). However, xerostomia is a frequent side eect.
e aim of this retrospective study was to evaluate salivary gland volumes
under/aer R(C)T.
Methods: 44 patients with HNC treated with RT or RCT at UKR between
2011 and 2015 were included. Median age was 62.5 years with 7.3%
female and 92.7% male patients. 11 patients obtained adjuvant treatment,
33 received primary R(C)T. 31 patients had concurrent RCT, while 13
received RT alone.
In all 44 patients, salivary gland volumes (Gll. parotideae and submandib-
ulares) were determined separately before start of RT, within 6 weeks aer
RT, and at follow-up periods (3,6, and 12 months aer RT) by volumetric
evaluation of imaging (CT and/or MRI).
Result: Volumes of salivary glands were signicantly smaller aer RT than
before RT at all times examined. Volumes of Gll. parotideae (mean -35%,
p < 0.0001) and Gll. submandibulares (-18%, p < 0.05) showed signi-
cant reduction within 6 weeks aer RT compared to volumes before RT.
Neither Gll parotis nor Gll submandibulares increased in volume within
12, 24 (n=9), nor 36 (n=3) months (p-values: 0.6 - 0.8).
Parotid glands showed no more signicant volume change over time more
than 12 months aer RT. Submandibular glands volumes were signi-
cantly lower aer 12 months compared to volumes aer 6 months post
RT. ere was a correlation between volume change of salivary glands and
mean dose arrived.
Discussion: Volumes of parotid and submandibular glands were signi-
cantly lower aer RT than before. Even up to 3 years aer therapy, salivary
gland volumes do no more increase signicantly. ese results are consis-
tent with correlation of xerostomia in patients aer RT.
Conclusion: e eects of RT on gland volumes result in changes of
patient anatomy that could be optimized during the course of therapy
by adaptive radiation planning. us, it would be possible to potentially
reduce the toxicity of therapy.
Disclosure Statement: e authors declare no conict of interest.
Indication of source:
1 https://doi.org/10.1007/s00066-021-01791-4
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 127
228
Challenges in recruiting of head and neck cancer patients to
participate in home exercise study
Sabine Felser1; Christian Junghanß1; Julia Rogahn1;
Daniel Fabian Strueder2; Brigitte Kragl1; Sabina Ulbricht3;
Christina Große-Thie1; East German Study Group of Hematology and
Oncology (Osho)4
1Rostock University Medical Center, Department of Medicine Clinic III,
Hematology, Oncology, Palliative Medicine, Rostock, Deutschland
2Rostock University Medical Center, Department of Otorhinolaryngology, Head
and Neck Surgery, Rostock, Deutschland
3Institute for Community Medicine, University Medicine Greifswald, Department
of Social Medicine and Prevention, Greifswald, Deutschland
4Ostdeutsche Studiengruppe Hämatologie und Onkologie e. V., Leipzig,
Deutschland
Background: Physical activity interventions are reported to bear con-
siderable benet for head and neck cancer patients (HNSCC pts). Some
studies have shown that HNSCC pts prefer exercise at home, alone and
with moderate intensity. To address this preferences we conceived a holis-
tic exercise program and evaluated the concept in a pilot study regarding
its feasibility and achieved eects1. In an ongoing multicenter study, this
exercise program is evaluated into a home based setting²,³. Preliminary
data show that the recruitment of 60 HNSCC pts is challenging. Herein
we analyzed characteristics of those consenting or not consenting to par-
ticipate in the study.
Methods: Direct response of HNSCC pts in tumor aercare consultation
including recording of interest in participation or reasons for refusal.
Result: Of 134 HNSCC pts surveyed (82% male), 12 expressed interest
(9%). Of these, eight (6%) consented to participate. ree additional
pts were included via a self-aid group. Of the currently included 11 pts
55% are female. e average age is 71 ± 7 years. Seven (64%) HNSCC pts
have a (technical) high school diploma. By self-report, seven (64%), are
non-smokers, three (27%) are ex-smokers, and one (9%) is a smoker. Nine
of 11 were active in sports before the disease. e main reasons for refusal
were “independently active” (N = 47), “no complaints” (N = 31), and “no
interest” (N = 23).
Conclusion: In sum, the recruitment rate is low. e HNSCC pts recruited
do not reect the typical HNSCC pts (male, smoker, lower educational
level). erefore, consideration should be given to using monetary incen-
tives to increase the motivation to participate.
Indication of source:
1 Felser S et al., Integrative cancer therapies 2020; 19: 1-12
2 Felser S et al., ONCOLOGY RESEARCH AND TREATMENT 2020; 43 (SUP-
PL 4): 134
3 DRKS-ID: DRKS00023883
Disclosure Statement: e authors declare no conict of interest.
262
Postoperative adjuvant radiochemotherapy (aRCH) with
cisplatin versus aRCH with cisplatin and pembrolizumab
in locally advanced head and neck squamous cell carcinoma -
the ADRISK trial
Susanne Wiegand1; Gunnar Wichmann1; Peter Brossart2; Holger Kaftan3;
Marc Münter4; Victor Lewitzki5; Nicole Rotter6; Georg Maschmeyer7;
Carmen Stromberger8; Thomas Gauler9; Ursula Schröder10;
Matthias Hautmann11; Martin Görner12; Orlando Guntinas-Lichius13;
Gunnar Hapke14; Bálint Tamaskovics15; Steen Dommerich16;
Anett Schmiedeknecht17; Andreas Dietz1
1Klinik und Poliklinik für Hals-Nasen-Ohrenheilkunde, Universitätsklinikum
Leipzig, Leipzig, Deutschland
2Med. Klinik IIII/ZIM, Hämatologie/Onkologie, Universitätsklinikum Bonn, Bonn,
Deutschland
3Klinik für Hals-Nasen-Ohrenheilkunde, Helios Klinikum Erfurt GmbH, Erfurt,
Deutshcland
4Klinik für Radioonkologie und Strahlentherapie, Klinikum Stuttgart -
Katharinenhospital, Stuttgart, Deutschland
5Klinik und Poliklinik für Strahlentherapie, Universitätsklinikum Würzburg,
Würzburg, Deutschland
6Hals-Nasen-Ohrenklinik, Universitätsklinikum Mannheim, Mannheim,
Deutschland
7Klinik für Hämatologie, Onkologie und Palliativmedizin, Ernst-von-Bergmann
Klinikum Potsdam, Potsdam, Deutschland
8Klinik für Radioonkologie und Strahlentherapie, Charite - Universitätsmedizin
Berlin, Berlin, Deutschland
9Klinik und Poliklinik für Strahlentherapie, Universitätsklinikum Essen, Essen,
Deutschland
10Klinik für Hals-, Nasen- und Ohrenheilkunde Campus Lübeck,
Universitätsklinikum Schleswig-Holstein, Lübeck, Deutschland
11Klinik und Poliklinik für Strahlentherapie, Universitätsklinikum Regensburg,
Regensburg, Deutschland
12Klinik für Hämatologie, Onkologie und Palliativmedizin, Klinikum Bielefeld,
Bielefeld, Deutschland
13Klinik für Hals-Nasen-Ohrenheilkunde, Universitätsklinikum Jena, Jena,
Deutschland
14Onkologisches Zentrum, Kath. Marienkrankenhaus gGmbH, Hamburg,
Deutschland
15Klinik für Strahlentherapie und Radiologische Onkologie, Universitätsklinikum
Düsseldorf, Düsseldorf, Deutschland
16Klinik für Hals-Nasen-Ohrenheilkunde, Charite - Universitätsmedizin Berlin,
Berlin, Deutschland
17Zentrum für Klinische Studien Leipzig, Medizinische Fakultät, Universität
Leipzig, Leipzig, Deutschland
Background: PD-1immune checkpoint inhibitors have been approved
as therapy in head and neck squamous cell carcinoma (HNSCC) as they
demonstrated a gain in overall survival (OS) in recurrent/metastatic dis-
ease. e next step is to explore the ecacy of immune checkpoint inhib-
itors in the curative setting. e aim is to describe herein the design and
rationale of the ADRISK trial, a prospective, multicenter, randomized
controlled phase II trial within the German Interdisciplinary Study Group
of German Cancer Society (IAG-KHT) of addition of pembrolizumab
to standard postoperative adjuvant cisplatin-based radiochemotherapy
(aRCH) in the treatment of patients with locally advanced intermediate-
and high-risk HNSCC.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts128
Methods: Patients with primary resectable stage III and IV HNSCC of
the oral cavity, oropharynx, hypopharynx and larynx with pathologic high
(R1, extracapsular nodal extension) and intermediate risk (R0 <5mm;
N≥2) aer surgery who are eligible for cisplatin-based aRCH aer surgery
will receive either standard aRCH with cisplatin versus the same treat-
ment + pembrolizumab (200 mg iv, in 3-week cycle, max. 12 months). e
objectives are to show that addition of pembrolizumab to cisplatin-based
aRCH improves event-free survival and OS compared with aRCH alone
in locally advanced intermediate and high-risk HNSCC. ADRISK will
recruit 240patients with advanced HNSCC in 16 centers to provide a pre-
cise survival estimate aer 24 months. Recruitment started in August 2018
and is ongoing (Trial registration: NCT03480672). Until March 2022, 158
patients were registered for the trial and 152 patients were randomized.
Discussion: Given the unmet need for reducing high rates of relapse in
intermediate-to-high-risk HNSCC patients by improved adjuvant treat-
ment, it is expected that ADRISK will provide new insights into treatment
in this setting and might demonstrate the ability of pembrolizumab to
improve survival of this patient group.
Disclosure Statement: e authors declare the following: wissenschaliche
Präsentationen, Mitarbeit in advisory Boards und Forschungsunterstützung durch
verschiedene Pharmarmen
352
Distress (DT) Monitoring in Head and Neck Cancer patients.
A feasibility study during surgical treatment
Sebastian Hoefert1; Annika Emmler1; Norbert Schäeler2; Siegmar Reinert1
1Universitätsklinikum Tübingen, Klinik- und Poliklinik für Mund-, Kiefer- und
Gesichtschirurgie, Tübingen, Deutschland
2Universitätsklinikum Tübingen, Psychosomatische Medizin und
Psychotherapie, Innere Medizin VI, Tübingen, Deutschland
Background: Certied Head and Neck Cancer Centres in Germany sup-
port patients with psychooncology. Usually, a distress (DT) assessment is
performed at the time of admission prior to therapy and psychooncology
support is provided at patients´ request.
Aim of this study was to measure DT at point of admission, before sur-
gery, aer surgery (end of intensive care unit) and before discharge to
analyse DT continuously.
Methods: Prior to surgical cancer therapy, psychooncological screening
is performed using the Tablet PC method. e test includes the NCCN
Distress ermometer (DT) and was measured again before surgery, aer
surgery, and before discharge to analyze the feasibility of DT measure-
ments and potential time points with high DT impact.
Result: A total of 49 patients were studied, 43% of whom were male. At
discharge, DT was minimally reduced in contrast to admission (1 point;
median). Patients with psycho-oncological support showed no signicant
dierence, except shortly aer surgery with reduced DT values in contrast
to patients without psychooncological support. DT measurement was
found to be helpful by most patients´ berits.
Discussion: Our study showed no signicant dierences in DT levels
during surgical treatment. In patients with psycho-oncological support,
there were no signicant dierences at the time of discharge, but signi-
cantly lower DT levels shortly aer surgery (end of ICU).
Conclusion: Our initial results demonstrate the feasibility of continuous
DT measurement and high stability of DT levels during surgical treatment.
Disclosure Statement: e authors declare no conict of interest.
430
Comparison between dierent lymph node predictors for
head and neck cancer: a population-based analysis of the
Thuringian cancer registries in Germany in 2009 and 2010
Mussab Kouka1; Elisa Al Ahmar1; Jens Büntzel2; Holger Kaftan3;
Daniel Böger4; Andreas Müller5; Stefan Schultze-Mosgau6; Thomas Ernst7;
Orlando Guntinas-Lichius1
1Universitätsklinikum Jena, Klinik für Hals-, Nasen- und Ohrenheilkunde, Jena,
Deutschland
2Südharzklinikum, Klinik für Hals-, Nasen- und Ohrenheilkunde, Nordhausen,
Deutschland
3Helios Klinikum Erfurt, Klinik für Hals-Nasen-und Ohrenheilkunde, Erfurt,
Deutschland
4SRH Zentralklinikum Suhl, Klinik für Hals-, Nasen- und Ohrenheilkunde, Suhl,
Deutschland
5SRH Wald-Klinikum Gera, Klinik für Hals-, Nasen- und Ohrenheilkunde , Gera,
Deutschland
6Universitätsklinikum Jena, Klinik für Mund-, Kiefer- und Gesichtschirurgie/
Plastische Chirurgie, Jena, Deutschland
7Universitätsklinikum Jena, Klinik für Innere Medizin II, Hämatologie und
Internistische Onkologie, Jena, Deutschland
Background: e aim of this population-based study was to compare and
evaluate the impact of dierent lymph node (LN) classication systems on
overall survival (OS) from head and neck cancer (HNC).
Methods: In this retrospective cohort study, data of all 401 patients
(median age: 57 years; 80% male, 47% stage IV) were included who were
diagnosed with HNC in 2009 and 2010 and were treated with neck dis-
section (ND) in uringian hospitals due to this diagnosis. Total num-
ber of lymph nodes removed (TNOD), number of positive lymph nodes
(PNOD), lymph node ratio (LNR) and log odds of positive lymph nodes
(LODDS) were comparatively analyzed regarding to OS.
Result: e average for the follow-up was 48 ± 32.1 months. e
average number of TNOD and PNOD in a unilateral ND were
13.6 ± 10.4 and 1.4 ± 2.7, respectively. e average number of
LNR and LODDS were 0.16 ± 0.27 and -0.96 ± 0.57, respectively.
In the multivariable analysis risk factors age > 57 years [hazard ratio (HR)
2.21; p = 0.007] and an advanced pT4 tumor stage [HR 3.38; 95% con-
dence interval (CI) 1.027 - 11.112; p = 0.045] were signicant. At the high-
est tumor stage, UICC stage IV, there was an increased risk of death [HR
9.218; 95% CI 2.721 - 31.224; p < 0.001]. PNOD as well as LNR showed no
independent inuence on OS while LODDS > -1.0 proved to be a signi-
cant independent predictor for OS with a 2.12-fold increased risk of death
[HR 2.120; 95% CI 1.129 - 3.982; p = 0.019].
Discussion: Recent studies have investigated the impact of LODDS on
HNC tumors in a single-institution study. In this study, LODDS was supe-
rior over the commonly used classication LNR and PNOD in a multi-in-
stitution analysis covering an entire federal state in Germany. Several
authors have set the LODDS cuto values very subjectively. A standard-
ization of the LODDS cuto values and a larger patient population in a
multinational clinical study are needed to conrm and validate our results.
Conclusion: In comparison to existing lymph node classication LODDS
was the best and independent node prognosticator for OS in HNC in a
real-world setting.
Disclosure Statement: e authors declare no conict of interest.
432
Exosomal serum biomarkers as predictors for laryngeal
carcinoma
Sarina Müller; Johannes Schuster; Olaf Wendler; Heinrich Iro;
Antoniu-Oreste Gostian
Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Deutschland
Background: Laryngeal carcinomas are the third most common head and
neck cancer. Whereas glottic carcinomas present themselves relatively
early with voice changes, especially localizations in the supra- and sub-
glottic regions lead to locally advances carcinomas at the time of diagnosis
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 129
in about 40% of the cases. Currently, there is no screening method and
diagnosis is dicult and can only be made by laryngoscopy. us, the
objective of this study was to identify exosomal serum biomarkers that
can diagnose laryngeal carcinomas and distinguish between early and late
stages.
Methods: IRB approved single center study of n=14 patients with laryn-
geal carcinomas (Stage I, Stage IV) and n=7 controls who all underwent
a panendoscopy for tumor staging and biopsy. A multiplexed proteomic
array (n=2000 proteins) on exosomes isolated from serum collected at the
day before surgery was performed. e most promising proteins for diag-
nosis and dierentiation were calculated using biostatistical methods and
were validated using Western Blots and Immunohistochemistry.
Results: TIE-1 (fold change (FC) 6.3) was the best protein to distinguish
between any stage of laryngeal carcinoma and control patients. PKLR (FC
10.2) was the most underexpressed protein in Stage IV compared to Stage
I whereas SOX 17 (FC 9.2) was the most overexpressed.
Discussion: All identied proteins have not been described before and
represent potentially novel biomarkers. However, those results have to be
validated in a second independent and larger cohort. Exosomal biomark-
ers show a superior signal-to-noise-ratio compared to whole serum and
therefore may be an important tool for non-invasive biomarker proling
for laryngeal carcinoma in the future.
Conclusions: TIE-1, PKLR and SOX17 have been identied as potential
novel biomarkers for the diagnosis of laryngeal carcinoma as well as dif-
ferentiation between dierent stages. Further studies are needed to vali-
date these results.
Disclosure Statement: e authors declare no conict of interest.
445
OncSaliva – a feasibility study with promising epigenetic
biomarkers for improved detection of head and neck cancer in
non-invasive specimen
Anna-Bawany Hums1; Carolin Dippmann1; Anne Hennig1; Lars Jansen2;
Matthias Dürst2; Martina Schmitz1; Alfred Hansel1; Orlando Guntinas-
Lichius3; Juliane Priese3
1oncgnostics GmbH, Jena, Deutschland
2Universitätsklinikum Jena, Klinik für Gynäkologie, Jena, Deutschland
3Universitätsklinikum Jena, Klinik für Hals-Nasen- und Ohrenheilkunde, Jena,
Deutschland
Background: Head and neck squamous cell carcinoma (HNSCC) are
mainly diagnosed at advanced tumor stage aer the onset of symptoms.
Timely detection would improve the options for successful treatment. We
identied and validated ve epigenetic markers in comparative studies
using primary HNSCC and healthy tissue. Aim of the current non-inter-
ventional OncSaliva study is to establish diagnostics of HNSCC including
saliva, swabs and tissue. Tumor marker detection is further monitored in
saliva and swabs postsurgery.
Methods: Five DNA methylation markers and a bisulte-specic ref-
erence were analyzed using fresh-frozen tissue, saliva or swabs from
HNSCC patients and controls. Samples were bisulte-converted before
use in methylation-specic multiplex QPCR. e goal is to include 100
controls and 100 HNSCC patients, the latter with 2-year follow-up exam-
ination until end of 2023.
Result: Until now 25 HNSCC and 7 control patients were included in the
study. e tumor marker ZNF671 was sensitively detected in HNSCC
tissue (21 samples positive) and associated saliva samples (19 samples
positive). One saliva sample was detected positive in the control group
for ZNF671, so far. Concordant results for ZNF671 (positive or nega-
tive) between both specimen from a single patient occurred in 17/25 for
HNSCC and 6/7 within controls. Swab examinations results are not yet
available. Data from individual patient follow-ups will be presented at the
congress.
Conclusion: Preliminary results from recent patient samples support our
study hypothesis to robustly detect HNSCC markers in both, tissue and
saliva. Utilization of saliva samples for cancer-specic diagnostic assays
based on epigenetic markers will be useful in in vitro diagnostics aiming
at secondary and tertiary prevention.
Disclosure Statement: e authors declare no conict of interest.
453
Therapy in HNC patients and nutrition – a patient centered
study
Andreas Cofre1; Stefanie Walter2; Jutta Huebner1; Jens Büntzel3
1Univrsitätsklinikum Jena, Hämatologie und internistische Onkologie, Jena,
Deutschland
2Bundesverband der Kehlkopfoperierten e.V., Bonn, Deutschland
3Südharzklinikum Nordhausen, Klinik für HNO Erkrankungen, HNO, Nordhausen,
Deutschland
Background: Most patients with head and neck cancers (HNC) are mal-
nourished, before diagnosis, due to the stomatognathic system being dis-
turbed at its onset. is paper questions how our patients experience their
treatment, the aermath and nutrition as a whole.
Methods: To formulate essential issues with nutrition aer HNC- treat-
ment we performed narrative interviews with members of the Federal
Association of Laryngectomy Patients and developed a questionnaire
comprising of 47 questions. We asked for, demographic data, weight his-
tory and side eects and oered multiple choice, visual scales, and free
text in a patient friendly way. It was handed to support groups and tumor
aercare patients for an intern validation and used statistical methods
such as the χ2-, sher- and the one way- Anova test.
Result e return rate was n=154 of which 36 identied as female and 88
as male. and had a median age of 65.5 years (39-86). e average time aer
treatment was 5.3 years (0.1-31).
We compared 3 endpoints with baseline weight: overall patients lost 7.8
% bodyweight aer the operation, 12.7% aer radio-chemotherapy and
gained 0.1% aer convalescence. Patients above 100 kg starting weight are
more likely to experience malnutrition while ending up with 17 % less
bodyweight aer convalescence (p<0.0001)
We asked for side eects like loss of smell (55.4%), dry mouth (56.3%),
dysphagia (57.1% ) and dental problems (33%) of which some were related
to a specic treatment (radiation and xerostomia) others reinforce each
other (xerostomia and dental problems). e analysis suggests a gradual
increase in adverse eects with the number of interventions performed.
For patients with only radiotherapy or surgery this dierence was signif-
icant (p < 0.0001).
Conclusion: Our patient centered data shows the correlation between
performed treatments and weight and therefore nourishment. In the sub-
group analysis, particularly heavier patients are at risk of malnutrition,
and we could show that more therapy also means more side eects.
Disclosure Statement: no conict of interest.
454
The impact of peritherapeutic antibiotics administration on the
oncological outcomes of head-and-neck squamous cell carcinoma
patients undergoing radiotherapy
Jiadai Zou1,2; Ilinca Popp1,2; Margaretha Glaser1; Lennard Halle1;
Andreas Knopf2,3; Anca-L. Grosu1,2; Nils Henrik Nicolay1,2;
Alexander Rühle1,2
1Klinik für Strahlenheilkunde, Universitätsklinikum Freiburg, Freiburg im
Breisgau, Deutschland
2Deutsches Konsortium für Translationale Krebsforschung (DKTK),
Partnerstandort Freiburg, Deutsches Krebsforschungszentrum (DKFZ),
Heidelberg, Deutschland
3Klinik für Hals-, Nasen- und Ohrenheilkunde, Universitätsklinikum Freiburg,
Freiburg im Breisgau, Deutschland
Background: Antibiotics administration can worsen the prognosis of
cancer patients receiving immune checkpoint inhibitors, potentially by
inuencing patients’ microbiome-immune system axis. We aimed to
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts130
evaluate the eects of antibiotic administration on the oncological out-
comes of head-and-neck squamous cell carcinoma (HNSCC) patients
receiving denitive (chemo)radiotherapy [(C)RT].
Methods: In a single-center analysis, 220 HNSCC patients who were
treated with (C)RT between 2010 and 2019 were analyzed, and infor-
mation about antibiotic application including indication, duration and
classes were taken from electronic patient records. Using t-tests and chi-
square tests, patient characteristics were compared depending on antibi-
otics usage. e impact of antibiotic prescription on the progression-free
(PFS) and overall survival (OS) was examined using Kaplan-Meier and
Cox analyses.
Result: 154 patients (70%) received antibiotics in a time interval ranging
between 30 days before (C)RT until completion of (C)RT. e median
duration of antibiotic application was 3 days (range, 1-49 days). While
93 (42%) patients obtained antibiotics during the 30 days prior to (C)RT,
100 (46%) were treated with antibiotics during (C)RT. e most common
indication was single-shot antibiotic prophylaxis prior to port catheter
implantation (n=132). ECOG status, age and radiotherapy dose did not
dier in patients treated with antibiotics. Peritherapeutic antibiotics use
deteriorated PFS (median 10 vs. 24 months, p<0.05, HR=1.40) and OS
(median 26 vs. 36 months, p<0.05, HR=1.41), while pretherapeutic usage
did not. In patients aged ≤75 years, antibiotic prescription during (C)RT
remained an independent variable for reduced PFS and OS in the multi-
variate Cox analysis.
Discussion: Prospective trials including microbiome analyses are required
to better understand the mechanisms behind the observed eects of anti-
biotics in HNSCC patients.
Conclusion: Peri- but not pretherapeutic antibiotics usage was associated
with reduced outcomes of HNSCC patients undergoing (C)RT.
Disclosure Statement: e authors declare no conict of interest.
458
Dysregulation of immune checkpoint molecules in oral cancer
Manuel Weber1; Rainer Lutz1; Jacek Glajzer1; Jan-Erik Werry1;
Christoph Baran1; Gesche Frohwitter1; Markus Eckstein2; Marco Kesting1;
Jutta Ries1
1Mund-, Kiefer- und Gesichtschirurgische Klinik Erlangen, Erlangen, Deutschland
2Pathologisches Institut, Erlangen, Deutschland
Background: An involvement of immune cell inltration and immune
regulation for the progression of oral squamous cell carcinomas (oscc)
is shown. Anti-PD1 therapy is approved for treatment of advanced oscc
cases and currently investigated for neoadjuvant use prior to denitive
surgery. e number of identied ccellular receptors with immune check-
point function is constantly increasing. A comparing analysis of a large
number of immune checkpoints in oscc is missing.
Methods: A Nano-String mRNA analysis was performed to assess the
expression of 21 immuno-regulatory checpoint molecules in 98 oscc
tumor samples and 41 healthy oral mucosa specimens.
Result: In oscc a signicantly increased expression of CD115, CD163,
CD68, CD86, CD96, GITRL and PD-L1 was detected. Additionally,
a marginally signicant increased CD8 expression was observed. e
expression of CD137L was signicantly downregulated in oscc compared
to healthy oral mucosa.
Discussion: Upregulation of the inhibitory CD96 receptor and PD-L1
ligand as well as the activating CD137L ligand could contribute to reduced
eector T-cell function and local immunosuppression in oscc. Increased
expression of the activating CD86 and GITRL could be explained by an
increased inltration of myeloid cells (CD115, CD68, CD163) and T-cells
(CD8) in oscc tissue.
Conclusion: e analysis contributes to the understanding of immune
escape in oscc and reveals potential targets for oral cancer immunotherapy.
Disclosure Statement: e authors declare no conict of interest.
476
Updated analysis of the phase II CheckRad-CD8 trial: First-line
treatment of locally advanced head and neck squamous cell
carcinoma with induction chemoimmunotherapy followed by
radioimmunotherapy
Markus Hecht1; Markus Eckstein2; Annett Kallies1; Jens von der Grün3;
Thomas Illmer4; Gunther Klautke5; Simon Laban6; Matthias Hautmann7;
Thomas Brunner8; Bálint Tamaskovics9; Axel Hinke10; Jian-Guo Zhou1;
Benjamin Frey1; Anna-Jasmina Donaubauer1; Ina Becker1; Sabine
Semrau1; Arndt Hartmann2; Panagiotis Balermpas3; Wilfried Budach9;
UdoGaipl1; Heinrich Iro11; Antoniu-Oreste Gostian11; Rainer Fietkau1
1Friedrich-Alexander-Universität Erlangen-Nürnberg,Strahlenklinik, Erlangen,
Deutschland
2Friedrich-Alexander-Universität Erlangen-Nürnberg, Pathologie
3Goethe-Universität Frankfurt am Main, Strahlentherapie, Frankfurt am Main,
Deutschland
4Gemeinschaftspraxis Hämatologie Onkologie, Arnoldstraße, Dresden, Dresden,
Deutschland
5Klinikum Chemnitz, Strahlentherapie, Chemnitz, Deutschland
6Universitätsklinikum Ulm, Hals-Nasen-Ohrenheilkunde, Ulm, Deutschland
7Universitätsklinikum Regensburg, Strahlentherapie, Regensburg, Deutschland
8Otto-von-Guericke-Universität Magdeburg, Strahlentherapie, Magdeburg,
Deutschland
9Heinrich-Heine-Universität Düsseldorf, Strahlentherapie, Düsseldorf,
Deutschland
10Clinical Cancer Research Consulting (CCRC), Düsseldorf, Deutschland
11Friedrich-Alexander-Universität Erlangen-Nürnberg, Hals-Nasen-
Ohrenheilkunde, Erlangen, Deutschland
Background: e trial studied induction chemoimmunotherapy followed
by radioimmunotherapy with double checkpoint inhibition aer CD8+
immune cell based patient selection.
Methods: Patients with stage III-IVB HNSCC were enrolled in this mul-
ticenter phase II trial. Study treatment consisted of a single cycle of cispla-
tin 30mg/m² d1-3, docetaxel 75mg/m² d1, durvalumab 1500mg x dose
d5 and tremelimumab 75mg x dose d5. Patients with increased intra-
tumoral CD8+ immune cell density or pathological complete response
(pCR) in the re-biopsy entered radioimmunotherapy up to a total dose
of 70Gy. Patients received further three cycles of durvalumab/tremelim-
umab followed by eight cycles of durvalumab mono (q4w). is updated
analysis was performed with data-cut o on June 7th 2021 (data-cuto for
rst analysis was January 17th 2021, presented at ASCO2021).
Result: Between September 2018 and May 2020, 80 patients were enrolled.
Median follow up was 17.2 months. Aer pathological patient selection,
60 patients entered radioimmunotherapy. In comparison to the rst anal-
ysis, the radioimmunotherapy cohort maintained a high progression-free
survival rate at one and two years of 78% and 72%, respectively, and an
overall survival rate at one and two years of 90% and 84%, respectively.
Furthermore, the entire cohort maintained a high progression-free sur-
vival rate at one and two years of 75% and 68%, respectively, and an overall
survival rate at one and two years of 87% and 79%, respectively.
Discussion: Induction chemo-immunotherapy followed by chemother-
apy-free radioimmunotherapy aer intratumoral CD8+ immune cell-
based patient selection has promising progression-free survival.
Conclusion: is treatment scheme is worth investigation in future clin-
ical trials.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 131
493
Combining surgery and immunotherapy in the treatment of
head and neck cancer – from neoadjuvant immunotherapy to
salvage surgery
Rainer Lutz1; Tjark-Ole Büntemeyer1; Manuel Olmos1; Jacek Glajzer1;
Jutta Ries1; Marco Kesting1; Manuel Weber1
1Universitätsklinikum Erlangen, Mund-, Kiefer- und Gesichtschirurgische Klinik,
Erlangen,
Background: Immunotherapy (IT) with checkpoint inhibitors is rou-
tinely used in advanced head and neck cancer when surgery and radia-
tion therapy are not available as curative treatment options. e use of IT
has shied to earlier stages in various malignancies. Patients undergoing
IT can potentially have long-term survival, thereby it can be dicult for
oncologic head and neck surgeons to assess the indication for surgery in
these patients.
Methods: We report on four exemplary cases in which surgery and IT
were successfully combined with dierent therapeutic intentions.
Result: In two cases with advanced oral cancer, neoadjuvant IT was per-
formed before surgical tumor resection with curative intent as an “individ-
ual cure attempt. Currently, both patients are alive and free of recurrence.
In two further cases, local progression occurred during palliative IT.
Tumor resection and microsurgical reconstruction were performed for
local symptom control. Patients survived 7 and 11 months aer surgery
with signicantly improved quality of life.
Discussion: As prospective studies are currently underway, neoadjuvant
IT before surgery may prove to be a valuable treatment for advanced head
and neck cancer with curative intent. Because patients with advanced
tumor disease may have long survival times under IT, palliative surgery
for symptom control should be critically evaluated in patients with pro-
gressive malignant tumors in good general health.
Conclusion: Surgery in combination with immunotherapy can be used as
neoadjuvant therapy in patients with advanced head and neck cancer as
well as to improve the quality of life of palliative patients.
Disclosure Statement: e authors declare no conict of interest.
512
Kinase Inhibitors of DNA-PK, ATM and ATR in Combination
with Ionizing Radiation Can Increase Tumor Cell Death in
HNSCC Cells While Sparing Normal Tissue Cells
Tina Jost1; Eva-Maria Faulhaber1; Julia Symank1; Julian Scheper1;
Felix Bürkel1; Rainer Fietkau1; Markus Hecht2; Luitpold V. Distel3
1Universitätsklinikum Erlangen, Strahlenklinik Erlangen, Strahlenbiologie,
Erlangen, Deutschland
2Universitätsklinikum Erlangen, Strahlenklinik Erlangen, Erlangen, Deutschland
3Universitätsklinikum Erlangen, Strahlenklinik Erlangen, Translationale
Immunonkologie, Erlangen, Deutschland
Background: Kinase inhibitors (KI) targeting components of the DNA
damage repair pathway are a promising new type of drug. Combining
them with ionizing radiation (IR), which is commonly used for treatment
of head and neck tumors, could improve tumor control, but could also
increase undesirable side eects on surrounding normal tissue.
Methods: e eect of KI of the DDR (ATMi: AZD0156; ATRi: VE-822,
dual DNA-PKi/mTORi: CC-115) in combination with IR on HPV-positive
and HPV-negative HNSCC and healthy skin cells was analyzed. Cell death
and cell cycle arrest were investigated using ow cytometry. Additionally,
clonogenic survival and migration behavior were examined.
Result: Studied HNSCC cell lines reacted dierently to DDRi. An increase
in cell death for all of the malignant cells could be observed when com-
bining IR and KI. Healthy broblasts were not aected by simultaneous
treatment. Migration was partially impaired. Inuence on the cell cycle
varied between the cell lines and inhibitors.
Discussion: In conclusion, a combination of DDRi with IR could be feasi-
ble for patients with HNSCC. Side eects on healthy cells are expected to
be limited to normal radiation-induced response. Formation of metastases
could be decreased because cell migration is impaired partially. e treat-
ment outcome for HPV-negative tumors tends to be improved by com-
bined treatment
Conclusion: In conclusion, we found that DDRi in combination with IR
more eectively inhibits tumor growth of HNSCC compared to the single
approaches and, most importantly, has a synergistic eect. e combina-
tion seems not to aect normal tissue surrounding the tumor more than
IR alone. Taken together, combined treatment has the potential to be a
therapeutic option that could improve tumor control without increasing
toxicity.
Reference:
1 Faulhaber, E.-M.; Jost, T.; et al. Kinase Inhibitors of DNA-PK, ATM and ATR
in Combination with Ionizing Radiation Can Increase Tumor Cell Death
in HNSCC Cells While Sparing Normal Tissue Cells. Genes 2021, 12, 925.
https://doi.org/10.3390/genes12060925
Disclosure Statement: e authors declare no conict of interest.
513
The role of plasma interleukin-6 as potential surrogate
parameter for tumor hypoxia in head-and-neck cancer
patients
Alexander Rühle1,2; Jamina T. Fennell1,2; Nicole Wiedenmann1,2;
Birgit Bieber1,2; Michael MIX2,3; Juri Ruf2,3; Raluca Stoian1,2; Dimos Baltas1,2;
Anca-L. Grosu1,2; Nils Henrik Nicolay1,2
1Klinik für Strahlenheilkunde, Universitätsklinikum Freiburg, Freiburg im
Breisgau, Deutschland
2Deutsches Konsortium für Translationale Krebsforschung (DKTK),
Partnerstandort Freiburg, Deutsches Krebsforschungszentrum (DKFZ),
Heidelberg, Deutschland
3Klinik für Nuklearmedizin, Universitätsklinikum Freiburg, Freiburg im Breisgau,
Deutschland
Background: Tumor hypoxia worsens the prognosis of head-and-neck
squamous cell carcinoma (HNSCC) patients receiving chemoradiation
(CRT). Fluorine-18 misonidazole PET ([18F]FMISO PET) can quantify
tumor hypoxia; however, as the logistic eorts of [18F]FMISO-PET are
considerable, we investigated the role of hypoxia-regulated interleukin-6
(IL-6) as potential surrogate parameter for tumor hypoxia.
Methods: 27 patients receiving denitive CRT within a prospective trial
were included in this analysis. Blood sampling and [18F]FMISO PET
were carried out in weeks 0, 2 and 5 of CRT. IL-6 plasma concentration
was determined using ELISAs. e ratio of tumor [18F]FMISO standard-
ized uptake value (SUV) to mean SUV within the contralateral sterno-
cleidomastoid muscle was calculated and dened as [18F]FMISO SUV
tumor-to-muscle ratio (T/M-ratio). Voxels within the primary tumor and
metastatic lymph nodes that exhibited a T/M-ratio ≥1.4 were summarized
as tumoral hypoxic subvolumes (HSV). e association between IL-6
and HSV was investigated using Pearsons correlations, and receiver-op-
erating characteristic analyses were conducted regarding the predictive
power of IL-6 for early tumor hypoxia response. e impact of IL-6 on
progression-free (PFS) and overall survival (OS) was investigated with
Cox analyses.
Result: IL-6 strongly correlated with the tumoral HSV at all analyzed
time points (week 0: r=0.775, p<0.001, week 2: r=0.553, p=0.007, week
5: r=0.734, p<0.001). e dierence in IL-6 levels between weeks 0 and 2
signicantly correlated with the tumoral HSV dynamics in this time inter-
val (r=0.533, p=0.011). ROC analyses revealed that IL-6 in week 2 pre-
dicted early tumor hypoxia response (AUC=0.822, p=0.031). Increased
IL-6 levels at week 5 were associated with reduced PFS (p=0.078) and OS
(p=0.013).
Discussion: IL-6 may serve as surrogate parameter for tumor hypoxia
dynamics in HNSCC patients undergoing CRT.
Conclusion: IL-6 plasma levels correlate with tumor hypoxia in HNSCC
patients.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts132
576
Patient-specic spheroids from squamous cell carcinoma of
the head and neck region (HNSCC) as a tool for personalized
therapy
Anne Lammert; Nicole Rotter; Johann Kern; Annette Aolter;
Sonja Ludwig; Esther Tenschert
Klinik für Hals-Nasen-Ohrenheilkunde, Kopf- und Halschirurgie,
Universitätsmedizin Mannheim, Mannheim, Deutschland
Purpose: Due to advances in the development of therapy regimes such
as targeted therapies/immunotherapies, cell culture techniques have also
become increasingly important, especially those that grow in 3D archi-
tecture. 3D cell culture models are particularly suitable for evaluating the
response to therapy in vitro, as they represent intercellular signaling mech-
anisms better than 2D cell cultures. Our goal is to develop patient-specic
spheroids that accurately represent the properties of the original tumor
tissue. Based on these, the response to dierent drugs could be evaluated
before use in patients in terms of “personalized medicine.
Methods: Four HNSCC cell lines (e.g. UMSCC-11A) were used to evalu-
ate optimal culture conditions for spheroid formation in co-culture with
stromal cells. Following tissue samples from HNSCC patients (n=14) were
processed to obtain single cell suspensions. e isolated cells were cul-
tured as spheroid monocultures and co-cultures. Furthermore immuno-
histochemistry (IHC) was performed to evaluate spheroids` expression of
dierent markers of interest (e.g. cancer stem cell markers).
Results: Cell culture protocols developed with the help of cell lines
could also be used for spheroid culture of tumor cells from HNSCC tis-
sue. However, we observed massive dierences between cells from dif-
ferent donors when brought into spheroid culture. Adding stromal cells
increased the reproducibility regarding size and stability of spheroids.
Viability assays showed an over 90% viability aer a week of incubation
and allowed for further testing of spheroids’ cellular structures with IHC
to investigate the arrangement pattern of cell types in comparison to
patients’ tissue.
Conclusions: e method of patient-specic squamous cell carcinoma
spheroids is established in our laboratory. HNSCC is a heterogeneous
entity with a very variable response to therapy. Cell culture models that
accurately represent the architecture of the original tumor are of great
importance on the way to “personalized medicine.
Disclosure Statement: e authors declare no conict of interest.
646
Co-culture with human mesenchymal stromal cells does
not inuence the in vitro radiosensitivity of head-and-neck
squamous cell carcinoma
Marie Lies1,1,2,2; Maren Strack1,2; Birgit Bieber1,2; Andreas R. Thomsen1,2;
Jochen Hess3,4; Andreas Knopf2,5; Anca-L. Grosu1,2; Nils Henrik Nicolay1,2;
Alexander Rühle1,2
1Klinik für Strahlenheilkunde, Universitätsklinikum Freiburg, Freiburg im
Breisgau, Deutschland
2Deutsches Konsortium für Translationale Krebsforschung (DKTK),
Partnerstandort Freiburg, Deutsches Krebsforschungszentrum (DKFZ),
Heidelberg, Deutschland
3Arbeitsgruppe Molekulare Grundlagen von HNO-Tumoren, Deutsches
Krebsforschungszentrum (DKFZ), Heidelberg, Deutschland
4Sektion Experimentelle und Translationale Kopf-Hals-Onkologie,
Universitätsklinikum Heidelberg, Heidelberg, Deutschland
5Klinik für Hals-, Nasen- und Ohrenheilkunde, Universitätsklinikum Freiburg,
Freiburg im Breisgau, Deutschland
Background: As mesenchymal stromal cells (MSCs) can aid regener-
ation of radiation-induced normal tissue toxicities, they could serve as
therapeutic agents for the attenuation of radiation-related sequelae in the
head-and-neck region. However, any radioprotective eects of MSCs on
head-and-neck squamous cell carcinoma (HNSCC) should be ruled out
prior to administration of MSC-based therapies.
Methods: Five human papillomavirus (HPV)-negative (UD-SCC5, FaDu,
Cal27, Detroit562, UD-SCC3) and one HPV-positive (UD-SCC2) HNSCC
cell lines were co-cultured with human bone marrow-derived MSCs. A
possible impact of direct and indirect MSC co-culture on the radiosen-
sitivity of HNSCCs was assessed using two- and three-dimensional sur-
vival, proliferation and viability assays. Radiation-induced alterations of
HNSCC cell cycle distribution and apoptosis rates in dependence of MSC
co-culture were examined with ow cytometry, whereas connective tis-
sue growth factor (CTGF) levels were determined using enzyme-linked
immunosorbent assays (ELISA).
Result: ere were no radioprotective eects of direct or indirect MSC
co-culture on HNSCCs in clonogenic survival, proliferation and viability
assays. Irradiation induced a dose-dependent G2/M arrest of HNSCCs at
96h that was not altered by MSC co-culture. Caspase-3 and annexin-V
measurements revealed a dose-dependent increase of radiation-induced
apoptosis in HNSCC samples irrespective of co-cultured MSC. CTGF lev-
els were signicantly increased in direct HNSCC-MSC co-cultures com-
pared to HNSCC mono-cultures, but comparable between the co-cultures
and MSC mono-cultures.
Discussion: ere are inconsistent data whether MSCs could increase
the radioresistance of tumor cells. Our comprehensive approach did not
reveal any radioprotective eects of MSCs on HNSCCs, therefore sup-
porting the usage of MSC-based treatments for the attenuation of radia-
tion-induced toxicities in HNSCC patients.
Conclusion: No radioprotective eects of MSCs on HNSCCs were
detected in a two- and three-dimensional in vitro approach.
Disclosure Statement: e authors declare no conict of interest.
739
Telomere length screening in young patients with head and
neck squamous cell carcinoma is suitable to detect underlying
inherited telomere biology disorders
Mareike Tometten1,2; Benjamin Rolles1,2; Maurice Klein2,3; Mark Ooms2,3;
Philipp Winnand2,3; Eva Simons2,4; Marcel Bourgeois1,2; Gerrit Spanier5;
Simon Laban6; Manuel Weber7; Carolin Goetz8; Falk Birkenfeld9;
Kim Kricheldorf1,2; Susanne Isfort1,2; Martin Kirschner1,2; Stephan
Hackenberg2,4; Frank Hölzle2,3; Fabian Beier1,2; Tim H. Brümmendorf1,2
1University Hospital RWTH Aachen, Department of Hematology, Oncology,
Hemostaseology and Stem Cell Transplantation, Aachen, Deutschland
2Center for Integrated Oncology, Aachen Bonn Cologne Duesseldorf (CIO-
ABCD), Köln, Deutschland, 3University Hospital RWTH Aachen, Department of
Oral and Maxillofacial Surgery, Aachen, Deutschland
4University Hospital RWTH Aachen, Department of Ear-, Nose- and Throat-
Medicine and Surgery of Head and Neck, Aachen, Deutschland
5University Hospital Regensburg, Department of Cranio-Maxillofacial Surgery,
Regensburg, Deutschland
6University Hospital of Ulm, Department of Ear-, Nose- and Throat-Medicine,
Ulm, Deutschland
7University Hospital of Erlangen, Department of Oral and Maxillofacial Surgery,
Erlangen, Deutschland
8Klinikum rechts der Isar, Technical University Muenchen, Department of Oral
and Maxillofacial Surgery, München, Deutschland
9University Hospital Schleswig-Holstein, Department of Oral and Maxillofacial
Surgery, Kiel, Deutschland
Background: Head and neck squamous cell cancer (HNSCC) aects
mainly males in 6th to 7th decade. Major extrinsic risk factors (RF) are
alcohol, tobacco and HPV-infection. A subset develops HNSCC at young
age <50years (y). Telomere biology disorders (TBD) are characterized by
impaired telomere maintenance and TBD patients (pts) are predisposed
to develop solid cancers arising at early age, amongst which HNSCC
represent the most frequent entity. Premature shortened telomere length
(TL) represents the functional TBD read-out. We systematically analyzed
TL in a young HNSCC pts cohort to identify unknown TBD cases.
Methods: For this sub-cohort, pts <50y at initial HNSCC diagnosis were
eligible. All pts were included in the Aachen telomeropathy registry
(ATR) based on clinical TBD suspicion. Lymphocyte (L) and granulocyte
(G) age-adjusted (aa) TL were analyzed by ow-FISH, next generation
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 133
sequencing (NGS) for telomere maintenance gene mutations performed
when TL found below the 1st percentile.
Result: Six German centers included 40 pts in this ongoing study. Mean
age at initial diagnosis was 42.0 ± 7.2y. Major site was oral tongue. Tumor
stage and RF available in 29 pts showed 18 (62%) with initial stage III or
IV, smoking in 13 (45%), alcohol abuse in six (20%) and 10 (34%) with no
history for both RF. AaTL in L was signicantly lower (-0.59 (p= 0.017))
compared to healthy controls, aaTL in G was normal (0.45 (p= 0,059))
representing premature aging. TL was below the 1st percentile both in L
and G in one patient. NGS screening revealed a homozygous gene muta-
tion suspected to cause TBD.
Discussion: Implementation of routine TL screening for TBD in young
HNSCC pts might improve the management because of expected excess
radiation and/or chemotherapy toxicity. Pre-aged lymphocytes could con-
tribute to tumor development due to chronic inammation or by being
part of a deleterious microenvironment.
Conclusion: TL screening in young HNSCC pts can identify underlying
inherited TBD. Further studies are needed to address the role of prema-
ture TL shortening in this pre-selected group.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
Health Economy/Public Health
Best-of-Abstract-Vortrag
415
How the corona pandemic aects cancer patients: Results
from a cross-sectional survey in Germany
Andrea Gaisser1; Rachel Eckford2; Volker Arndt3; Michael Baumann4;
Evelyn Kludt5; Katja Mehlis6; Jasper Ubels2; Eva Winkler6;
Susanne Weg-Remers1; Michael Schlander2
1Krebsinformationsdienst, Deutsches Krebsforschungszentrum, Heidelberg,
Deutschland
2Gesundheitsökonomie, Deutsches Krebsforschungszentrum, Heidelberg,
Deutschland
3Abt. Klinische Epidemiologie, Deutsches Krebsforschungszentrum, Heidelberg,
4Wissenschaftlicher Vorstand, Deutsches Krebsforschungszentrum, Heidelberg,
5Krebsinformationsdienst, Deutsches Krebsforschungszentrum, Heidelberg,
6Klinik für Medizinische Onkologie, Nationales Centrum für Tumorerkrankungen,
Heidelberg, Deutschland
Background: e COVID-19 pandemic required to prioritize health care
services, potentially aecting the care for other vulnerable patients, such
as those with cancer. Beyonduncertaintywith regard to their care and
their risk of infectionpatients mayalso experience psychosocial or other
types of burden. e aim of this pilot survey study is to investigatehow the
pandemic aects medical care of cancer patients and their psychosocial
well-being.
Methods: We surveyed a convenience sample of cancer patients who
contacted the German Cancer Information Service (KID) via e-mail with
questions between July 2020 and June 2021. Using an anonymized online
questionnaire, informationoncancer type and phase, changes incancer
care and pandemic related worries was collected. Anxiety and depression
were assessed using the Hospital Anxiety and Depression Scale (HADS). 
Results: Of 718 responses, 621 were evaluable. Median age of participants
was 60 years, 76.3% were women, and breast cancer was the most fre-
quent cancer type (51.1%). e majority of patients had completed initial
treatment (40%). Overall 12.9% (n=79) of patients reported changes in
their medical care, mostly to follow-up appointments. 33% had consider-
able worries that the pandemic might aect their quality of care, and over
80% missed personal social contacts quite a bit or very much. Near one
h of respondents worried about their jobs and possible nancial losses.
Prevalence of anxiety and depression was 55% and 39%, respectively.
Discussion: Results show that patient well-being and care have been
aected by the corona pandemic.Most patients received their treatment
as planned, but psychological burden in terms of worries, anxiety and
depression was high across the survey period, covering the months aer
wave 1, wave 2 and wave 3.
Conclusion: Our results underscore cancer patients´ psycho-social bur-
den caused by the pandemic. Health care organisationsmust be aware of
this and ascertain equitablecare and services as needed for all patients
particularly in times of crisis.
Disclosure Statement: e authors declare no conict of interest.
1016
Long-term benets, harms and cost-eectiveness of dierent
screening strategies for individuals with familial colorectal
cancer risk in Germany – a decision analysis within the
FARKOR study
Gaby Sroczynski1; Lára R. Hallsson1; Nikolai Mühlberger1; Beate Jahn1,2;
Sabine Homann3; Raphael Rehms3; Doris Lindörfer3; Alexander Crispin3;
Ulrich Mansmann3; Uwe Siebert1,2,4,5
1Institute of Public Health, Medical Decision Making und Health Technology
Assessment, UMIT - University for Health Sciences, Medical Informatics and
Technology, Hall i. T., Österreich
2Division of Health Technology Assessment, ONCOTYROL Center for
Personalized Cancer Medicine, Innsbruck, Österreich
3Institute for Medical Informatics, Biometry and Epidemiology, Ludwig-
Maximilians University, Munich, Österreich
4Center for Health Decision Science, Departments of Epidemiology and Health
Policy & Management, Harvard T. H. Chan School of Public Health, Boston, USA
5Institute for Technology Assessment and Department of Radiology,
Massachusetts General Hospital, Harvard Medical School, Boston, USA
Background: To evaluate the benet-harm balance and cost-eectiveness
of dierent screening strategies using colonoscopy or immunologic fecal
blood testing (iFOBT) in German individuals younger than age 50 with
familial colorectal cancer (CRC) risk.
Methods: A Markov-state-transition model simulating CRC progression
was developed to evaluate various screening strategies diering in screen-
ing test, interval, and age at start and end. We used German clinical, epi-
demiological, and economic data (€2020) along with test accuracy data
from meta-analyses. We adopted the German statutory health insurance
perspective and discounted eects and costs at 3% annually. Evaluated
outcomes included life-years gained (LYG), severe complications (SC)
associated with colonoscopy, incremental harm-benet ratios (IHBR
[SC/LYG]), and incremental cost-eectiveness ratios (ICER [€/LYG]).
Comprehensive sensitivity analyses were performed.
Result: In the base-case analyses (full compliance), IHBRs for iFOBT
screening were 0.00054 (biennial, age 45-65), 0.0014 (biennial, age 35-65),
0.0024 (biennial, age 30-70) and 0.0135 (annual, age 30-54; biennial,
age 55-75) SC/LYG. Corresponding IHBRs for 10-yearly colonoscopy
were 0.001 (age 55-65), 0.004 (age 45-65), 0.006 (age 35-65) and 0.012
(age 30-70) SC/LYG. Compared to standard care, biennial iFOBT age
35-75 was cost-saving. e next more eective iFOBT strategies yielded
ICERs of 2,630 €/LYG (biennial, age 30-70), and 34,675 €/LYG (annual,
age 30-54; biennial, age 55-75), respectively. Compared to standard care,
10-yearly colonoscopy age 45-65 was cost-saving. Moving to earlier start
and later stop yielded ICERs of 2,962, 3,240 and 9,279 €/LYG for 10-yearly
colonoscopy screening at age 40-70, 35-65, and 30-70, respectively.
Conclusion: Oering colonoscopy or iFOBT screening to individuals
younger than age 50 with familial CRC risk can be considered benecial
and cost-eective in the German context. Benet-harm ratios suggest
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts134
10-yearly colonoscopy or alternatively biennial iFOBT from age 30 to 70
to be acceptable.
Disclosure Statement: e authors declare the following: is work was supported
by GB-A Innovationsfonds Grant: 01NVF17026.
Poster
44
Urban deprivation and health services uptake: the example of
genetic counselling at the Cologne Centre for Familial Breast
and Ovarian Cancer
Anja Tüchler1, Robert Rémy1, Kerstin Rhiem1, Rita K. Schmutzler1,
Timo-Kolja Pförtner2
1Zentrum Familiärer Brust- und Eierstockkrebs, Uniklinik Köln, Centrum für
integrierte Onkologie (CIO), Köln, Deutschland
2Institut für Medizinsoziologie, Versorgungsforschung und
Rehabilitationswissenschaft, Universität zu Köln, Köln, Deutschland
Background: As the eld of personalized medicine continues to grow,
social inequalities in the use of these health services need to be addressed,
as a social gradient for the utilization of health services has been observed.
We present rst data on socioeconomic dierences in the uptake of genetic
counselling in the German health care setting, using patient data from the
Cologne Centre for Familial Breast and Ovarian Cancer.
Methods: Data from patients with a residential address in Cologne
were assigned to their respective city district (n = 86). Empirical Bayes
Smoothed (EBS) uptake rates per 1.000 inhabitants were calculated for
each district and used as dependent variable in bivariate spatial ordinary
least squares (OLS) regression models. An index for multiple urban depri-
vation for the city of Cologne, migration levels and mean age per city dis-
trict were used as explanatory variables.
Result: Data of 3,109 patients were considered for this analysis. City dis-
trict level EBS-rates ranged from 1.54 – 4.54 patients per 1.000 inhab-
itants, mean EBS-uptake rate was 2.83 (95% condence interval 2.69
– 2.96). Bivariate OLS spatial regression models revealed migration (R² =
0.499) and multiple deprivation (R² = 0.574) as suitable explanatory fac-
tors for the variance in uptake rates.
Discussion: Substantial dierences in the uptake of genetic counselling
services were observed in the city of Cologne. ese dierences were
shown to be closely related to area-based deprivation and migration levels.
Conclusion: Our results indicate that the social gradient in health care
utilization observed in numerous health care contexts also exists in the
context of familial and hereditary breast and ovarian cancer.
Disclosure Statement: e authors declare no conict of interest.
238
Regional quality conferences of the Hamburg Cancer Registry
(HCR): Evaluation of guideline-based treatment pathways
using the example of radiotherapy after breast-conserving
surgery in patients with invasive breast cancer
Vera Henrichs1; Annemarie Schultz2; Imma Löhden2; Cynthia Erb2;
Alice Nennecke2
1Hochschule für Angewandte Wissenschaft Hamburg, Hamburg, Deutschland
2Freie und Hansestadt Hamburg, Behörde für Wissenschaft, Forschung,
Gleichstellung und Bezirke, Hamburgisches Krebsregister, Hamburg ,
Deutschland
Background: Regional quality conferences of the Hamburg Cancer
Registry (HCR) aim to promote interdisciplinary collegial discussion on
data to further improve quality of oncological care.
According to the current S3 guideline on breast cancer, postoperative
radiotherapy (RT) is the key intervention to reduce the risk of intrama-
mmary recurrence in context of breast-conserving therapy (BCT). As
part of regional quality conferences it was shown that fewer patients than
expected received RT aer BCT in Hamburg. Additional analyses were
performed to verify this statement.
Methods: HCR-registered patients diagnosed with invasive breast can-
cer from 2017 to 2020 with BCT followed by adjuvant RT or not were
included. e observation period encompassed Jan. 1, 2017, through
March 30, 2021.
Result: 76.8% (2,569) of 3,347 patients with invasive breast cancer and
BCT received RT during the observation period in Hamburg. Concerning
23.2% (778) of patients, no evidence of RT was provided.
In Kaplan-Meier analysis, overall survival was signicantly better in
patients with BCT and adjuvant RT compared to patients without RT
(96.2% vs. 89.6% by end of observation; p < .0001, log-rank test). Receiving
adjuvant RT reduced the risk of mortality by 56.6% in patients aer BCT
(HR = .434; 95% CI .265 - .712; p = .001).
Conclusion: Our results indicate that the majority of patients with inva-
sive breast cancer and BCT diagnosed in Hamburg received adjuvant RT
according to guidelines. A quarter of patients lack this evidence, while this
proportion was estimated 10% - 15% by clinicians. As expected, the pos-
itive impact of RT on survival of patients with invasive breast carcinoma
and BCT was conrmed.
In context of the regional quality conferences, decits in care can be
revealed and further research is necessary to investigate reasons for
undertreatment.
Disclosure Statement: e authors declare no conict of interest.
278
Regional dierences in the access to certied cancer care –
The inuence of regional innovation systems in Germany
Tim Brand; Katharina Blankart
CINCH Health Economics Research Center, Universität Duisburg-Essen, Essen,
Deutschland
Background: A central aspect of improving quality of care is the diusion
of innovation from research into practice. One way to facilitate this pro-
cess is program accreditation. By conceptualization, innovation activities
and accreditation require dierent competencies and processes. While
this may hinder the uptake of accreditation, the eect of innovation activ-
ities on the diusion of accreditation is mostly unknown. In this study, we
aim to evaluate this relationship in the context of accredited organ cancer
centers in Germany.
Methods: We perform a retrospective study at district level combining
scientic publications as measures for innovation activities and accred-
itation data for eight cancer sites from 1998-2017. Scientic publication
data was obtained from the National Library of Medicine and mapped to
the authors’ geolocation using the MapAl tool. Regional accreditation
status and timing is provided by the German Cancer Society. We evaluate
the eect of innovation activities on accreditation status, estimating linear
probability models including accreditation type xed eects. We consider
cancer incidence, gross domestic product and hospital competition as
confounders of innovation activities.
Results: Regions with any publications have a 9.6% higher probability to
have at least one accredited cancer center. Sub-group analysis for breast
cancer suggests that about 60% of districts had no breast cancer publi-
cations before initiation of the accreditation program. In comparison to
these district, districts with up to 20 publications (90th percentile) had
on average 0.174 accredited centers more one year and 0.25 centers more
three years aer initiation. Districts in the highest 10% by publication
activity had on average 0.377 accredited centers more one year and 0.846
centers more three years aer initiation.
Discussion: Innovation activities and accreditation are no contradictory
strategies in specialized cancer care. New incentives for accreditation
might increase quality of cancer care in regions with fewer innovation
activities.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 135
449
Low rates of inuenza and pneumococcal vaccination among
cancer patients
Simon Lendowski1; Corinna Sophie Marheinecke2; Daniel R. Quast3;
Eleni Kourti1; Stephanie Pfänder2; Anke Reinacher-Schick1; Oliver Overheu1
1Klinik für Hämatologie und Onkologie mit Palliativmedizin, St. Josef-Hospital
Bochum, Klinikum der Ruhr-Universität Bochum, Bochum, Deutschland
2Abteilung für Molekulare & Medizinische Virologie, Ruhr-Universität Bochum,
Bochum, Deutschland
3Klinik für Innere Medizin, St. Josef-Hospital Bochum, Klinikum der Ruhr-
Universität Bochum, Bochum, Deutschland
Background: Cancer patients, especially those under chemotherapy, are
at an increased risk for respiratory infections, including inuenza and
pneumococcal infections, which are both vaccine preventable. However,
low vaccination rates have been reported.1
Methods: Between April and August 2021 125 cancer patients at our
university cancer center completed a questionnaire containing multiple
choice questions and ten eleven-level Likert items ranging from 1 (“totally
disagree”) to 11 (“totally agree”) in order to assess rates of previous inu-
enza and pneumococcal vaccinations as well as the patients attitudes
towards vaccinations in general.
Result: Mean age was 65.5 years (24-86), 46% were female. e majority
(82%) had solid tumors. Almost all (88%) were on active anti-tumor ther-
apy, mainly chemotherapy (75%). 58% received an inuenza vaccination
at least once within the last 5 years, whereas only 30% had a pneumococcal
vaccine. Rate of inuenza vaccination among women was statistically sig-
nicant higher (70% vs. 48%, p=0.0064), while it did not dier in regard of
pneumococcal vaccine (28% among men vs. 35% among women, p=0.21).
Most patients completely disagreed with “being against vaccinations in
general” (80%; mean 1,81; statistically signicant dierence on Likert item
between men vs. women: mean 1.45 vs. 2.26, p=0.0427).
Discussion: We report higher rates of vaccination against both inuenza
and pneumococcal infections than previous studies. Nonetheless, rates
remain low, especially among men.
Conclusion: Further research is necessary regarding factors associated
with hesitancy to receive vaccinations as well as to determine potentials of
improvement of vaccine coverage. Also gender dierence should be taken
into account.
Reference:
1 Monier A, Puyade M, Hernanz MPG, Bouchaert P, Leleu X, Tourani JM, et al.
Observational study of vaccination in cancer patients: How can vaccine covera-
ge be improved? Med Mal Infect. 2020;50(3):263-8.
Disclosure Statement: e authors declare no conict of interest.
473
Perception and expectations of preventive health behavior
in medical institutions during the SARS-CoV-2 pandemic
in Germany: Results of a cross-sectional web-based survey
in women with an increased hereditary risk for breast and
ovarian cancer
Roxana Schwab; Annika Droste; Annette Hasenburg
University Medical Center Mainz, Department of Gynecology and Obstetrics,
Mainz, Deutschland
Background: Patients with cancer are at higher risk to be infected by
SARS-CoV-2, are more likely to develop a severe COVID-19 illness, and
are more likely to die as a result of COVID-19. us, several strategies
were proposed to mitigate the SARS-CoV-2 pandemic crisis with respect
to people at higher risk, such as implementing strict personal precautions
in cancer patients or cancer survivors.
Methods: To assess the expectations and perspectives of women with an
increased hereditary risk for breast and ovarian cancer regarding mea-
sures to prevent infection and implement environmental control during
the SARS-CoV-2 pandemic, a web-based survey was placed on internet
platforms of support groups between 29th January and 22th April 2021.
Missing data were composed of those patients who did not answer the
question or who did not have a clear opinion regarding the topic. Data are
presented as frequencies of selected items.
Result: 37.5% of participants stated, that they would like to be informed
about the hygiene concept of the health care institution and 20.3%
reported that this information would have changed their own behavior.
To prevent the spread of the virus, 57.8% of respondents approved testing
of patients previous to a visit to a health care facility and 95.3% stated,
that health care professionals should be tested on a regular basis. 93.8%
approved the change of appointments to ensure social distancing, but
75.0% would support the possibility to be escorted by a signicant other
during medical appointments. To avoid unnecessary possible exposure,
71.9% of participants endorsed the possibility of virtual patient consulta-
tions. Additionally, 84.4% of respondents expected, that health care per-
sonnel used at least surgical masks, and 68.8% expected, that the health
care personnel used FFP-2 masks.
Discussion: Protecting patients at risk and medical caregivers is a priority
during pandemics.
Conclusion: Our data emphasize the wish and need for reorganization of
health care facilities with the aim to protect patients at risk.
Disclosure Statement: e authors declare the following: RS: Honoraria: Roche
Pharma AG, AstraZeneca, Streamedup!GmbH, AH: Honoraria: AstraZeneca;
Celgen; MedConcept GmbH, Med update GmbH; Medicultus; Pzer; Promedicis
GmbH; Soconsult; Roche Pharma AG; Streamedup!GmbH; Tesaro Bio Germany
GmbH, LEO Pharma Ad Board; PharmaMar; Promedicis GmbH; Roche Pharma
AG; Tesaro Bio Germany GmbH, AstraZeneca, LEO Pharma, MSD Sharp &
Dohme GmbH
523
Real world data (RWD) from the AIO ColoPredict Plus (CPP)
registry (AIO-KRK-0413/ass): Impact of the Sars-CoV-2
pandemic on enrollment of patients (pts.) with colorectal
cancer (CRC) - analysis for the CancerCOVID consortium
Celine Lugnier1; Anna-Lena Kraeft2; Sabine Sommerlatte3; Inke Feder4;
Daniel Benitez2; Eleni Kourti2; Rabia Safaei2; Sarah Wisser4; Olaf Schoer5;
Vitali Heidt6; Wolfgang Knauf7; Christan Teschendorf8; Waldemar Uhl9;
Stefanie Nöpel-Dünnebacke2; Jochen Schmitt10; Jan Schildmann11;
Anke Reinacher-Schick2; Andrea Tannapfel4
1Bochum, St. Josef Hospital Bochum, Ruhr Universität Bochum, Mediznische
Klinik V für Hämatologie und Onkologie mit Palliativmedizin, Bochum,
Deutschland
2Katholisches Klinikum Bochum, St. Josef Hospital Bochum, Ruhr Universität
Bochum, Mediznische Klinik V für Hämatologie und Onkologie mit
Palliativmedizin, Bochum, Deutschland
3Institut für Geschichte und Ethik der Medizin, Medizinische Fakultät der Martin-
Luther Universität Halle-Wittenberg, Uniklinikum Halle, Halle
4Institut für Pathologie - Georgius Agricola Stiftung Ruhr, Institut für
Pathologie - der Ruhr-Universität Bochum am Berufsgenossenschaftlichen
Universitätsklinikum Bergmannsheil , Bochum
5Zentrum für evidenzbasierte Gesundheitsversorgung, Universitätsklinikum und
Medizinische Fakultät Carl Gustav Carus der Technischen Universität Dresden,
Dresden
5Wissenschaftliche Institut der Niedergelassenen Hämatologen und
Onkologen– WINHO GmbH, Köln
7Berufsverband der Niedergelassenen Hämatologen und Onkologen in
Deutschland e.V., Köln
8St. Josef Hospital Dortmund, Mediznische Klinik I, Dortmund
9Katholisches Klinikum Bochum, St. Josef Hospital Bochum, Ruhr Universität
Bochum, Allgemin- und Viszeralchirurgie, Bochum
10Zentrum für Evidenzbasierte Gesundheitsversorgung, Universitätsklinikum
und Medizinische Fakultät Carl Gustav Carus an der Technischen Universität
Dresden, Dresden
11Institut für Geschichte und Ethik der Medizin, Medizinische Fakultät der Martin-
Luther Universität Halle-Wittenberg, Uniklinikum Halle, Halle
Purpose: CRC prognosis has improved through guideline-based care.
COVID-19 pandemic lead to re-allocation of health care resources poten-
tially putting sections of cancer care at a disadvantage. We compared
enrollment and clinical subgroups into our registry before and during the
rst (fw) and second wave (sw) of the COVID-19 pandemic.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts136
Methods: CPP assembles clinical, histo-pathological and molecular
data of pts. with resected CRC. Prospectively enrolled pts. during the
fw (4-6/2020) and the sw (10-12/2020) were analyzed, focusing on total
numbers, age and sex compared to corresponding pre-pandemic intervals
of 2019. Due to site expansion (70 to 161) of CPP we calculated quarterly
counts per site and in relation to total enrollment.
Results: 2221 pts. enrolled into CPP during 2019 and 2020 were included,
47 % female (F) /53 % male (M). Mean age in 2019 was 71.9 years (y) vs
71.6 y in 2020. Mean number of pts. enrolled in CPP with primary diag-
nosis of CRC per site 2019/2020: fw 8,5/6.9 and sw 6.2/5.8. Evaluation for
age showed: 2019%/2020% fw >70 y was 52.5/53.5 and ≤70 y 47.5/ 46.5
respectively; for the sw > 70 y was 45.6/ 53.5; ≤70 y 54.4/46.5. M vs F in fw
2019%/2020% M 50.5/61; F 49.5/39; in sw M 57.6/56; F 42.4/44.
Discussion: CPP did not detect substantial dierences in total counts of
enrolled patients or distribution of age and sex. We detected a slight dip
in enrollment together with a small shi toward men in fw as well as to
elderly pts. in sw. Enrollment of pts. into registries seems to be feasible
even in pandemic situation. Potentially, a possible data bias as preference
of registry enrollment over randomized controlled trials.
Conclusion: Real world data from CPP must be complemented by addi-
tional data for comprehensive assessment of colon cancer care and will
be complemented for nal data presentation in 2022 with data collected
during the third and omicron wave.
is study was supported by the Federal Ministry of Education and
Research
Disclosure Statement: e authors declare no conict of interest.
562
Evaluation of an interventional retrospective study with
oncological training and exercise therapy (OTT) in a health
insurance care contract
Louisa Zimmermann1; Nico De Lazzari1; Freerk Baumann2; Habibe Ercan3;
Sara Man2; Christoph Meyer4; Marion Hammling5; Mitra Tewes1
1Westdeutsches Tumorzentrum, Innere Klinik (Tumorforschung),
Universitätsklinikum Essen
2Centrum für Integrierte Onkologie Aachen Bonn Köln Düsseldorf, Klinik I für
Innere Medizin Onkologie, Universität zu Köln
3Klinik für Psychosomatische Medizin und Psychotherapie , LVR Klinikum Essen,
Universität Duisburg Essen
4Praxiszentrum Elisengalerie, Aachen
5AOK Rheinland/Hamburg
Purpose: To evaluate the cost-eectiveness of the oncological training
and exercise therapy (OTT) in this retrospective interventional study on
cancer patients (pts) on curative and palliative therapy protocols.
Methods: Data provided by a German healthcare provider. Number and
cost of ambulant visits, days and cost of hospitalization, and costs of med-
ication of enrolled pts and a matched control group (CG) were collected
for 9-months aer the begin of the training intervention. Demographics
and diagnoses were documented over the whole 4-year study period. Pts
completing at least 12 of 24 planned training sessions were dened as
intervention group (IG).
Results: From 2015 to 2019 152 pts were recruited for OTT participation.
Of these, 39 completed the intervention, 19 dropped out during training
and 94 enrolled but never participated. Most frequent malignancies were
breast (IG/ CG; 20.5 / 26.9%) and lung cancer (20.5 / 12.8%), and hema-
tological malignancies (20.5 / 15.4%). We observed a tendency towards
better survival in the IG compared to the CG (1-year-survival 94.9 /
78.7%). e IG had a signicantly higher number of ambulant visits and
higher associated costs than the CG (median dierence 371 - 630€ | 8 - 5d;
p<0.0001 - p=0.0069). Furthermore, the IG had signicantly higher costs
of medication (median dierence 265€; p=0.007). e number of inpa-
tient days and costs of hospitalization did not dier signicantly between
groups.
Discussion: e OTT might improve patient mobility, compliance and
therapeutic relationship, as the number of ambulant visits, associated
costs, and cost of medication increased under OTT. is might explain a
tendency towards better survival in the intervention group, although the
need for in-hospital care was not decreased correspondingly.
Conclusions: Tumor patients participating in structured physical training
seek more outpatient medical care without the need for more frequent
hospital admission. e OTT might thus improve compliance and thera-
peutic relationship which might improve morbidity and mortality.
Disclosure Statement: e authors declare the following: Koautoren sind Teilneh-
mer des wissenschalichen Beirates der Krankenkasse.
779
Treating hepatocellular carcinoma (HCC) in Germany – an
health economic perspective
Bernhard Mörtl1,1; Dominik Beier2; Enroci N de Toni3;
Korbinian Hasselmann1; Stefan Munker3; Karin Berger1;
Benedikt Westphalen1
1Klinikum der Universität München (LMU), Medizinische Klinik und Poliklinik III,
München, Deutschland
2InGefInstitute for Applied Health Research Berlin GmbH, Berlin, Deutschland
3Klinikum der Universität München (LMU), Medizinische Klinik und Poliklinik II,
München, Deutschland
Background: Only limited information on epidemiology, resource
consumption, costs from third party payer perspective, and outcomes
observed in routine care (inpatient and outpatient) in Germany exists.
Objective of this study was to evaluate the grade claims data can be used
to ll aforementioned gaps.
Methods: is retrospective cohort study is based on anonymized, lon-
gitudinal German third party payer claims data from 2014 - 2019 (InGef
database). Inclusion criteria: ≥18 years, inpatient / outpatient diagnosis of
HCC (ICD-10-GM C22.0).
Result: In total 818 prevalent patients (pts) with hepatocellular carcinoma
were identied in 2014, 994 pts in 2019. In this cohort the prevalence per
100.000 increased to 29 pts in 2019, compared to 24 pts per 100.000 in
2014. Mean age was 70 years (SD ±10,7), 73% were male. Approximately
86% pts were hospitalized, with mean 3 admissions (SD ±2,7) annually
and mean 32 inpatient days per patient (ppt; ±41,6). Mean annual total
costs were €20.184 ppt in 2014 (median 13.652; range 112 – 213.877) and
€22.935 ppt in 2019 (15.474; 134 – 482.238). Proportion of costs in 2019
exemplary: inpatient care (59%), drug treatment (29%), outpatient care
(8%) and therapeutic aids (4%). In the context of increasing patient num-
bers, the total cost for this cohort increased from €16.5 Mio in 2014 up to
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 137
€22.8 Mio in 2019. e mean annual mortality of the prevalent pts was
30,6%. In a subgroup analysis on incident HCC pts, 67% died within the
rst two years aer diagnosis.
Discussion & Conclusion: e clinical outcome in terms of survival is
poor. Mortality, frequency and length of hospitalization signal a high bur-
den on patients and their families. e level of information provided by
claims data is limited as for example the information on number of treat-
ment lines or tumour status are missing. Despite these limitations, claims
data give a detailed insight into epidemiology, hospitalisation, resource
consumption, costs and mortality of the study cohort.
Disclosure: LMU received a research grant from Roche Pharma AG;
InGef received research funding by LMU.
Disclosure Statement: e authors declare the following: LMU Klinikum (MED
III) received a research grant from Roche; InGef has received research funding by
LMU Klinikum (MED III).
986
On the eects of patient pathways in comprehensive cancer
care - A systematic literature review of evaluation criteria
Peggy Richter1; Lisa Zapfe1
1Technische Universität Dresden, Forschungsgruppe Digital Health, Dresden,
Deutschland
Background: Patient pathways (PPs) are perceived helpful to coordinate
comprehensive cancer care, implement guideline recommendations and
inform patients. e updated S3-guideline for pancreatic cancer now
includes a PP template for pancreatic cancer centers. To advance PP appli-
cation and study their impacts, reliable evaluation criteria are needed.
is study analyses which evaluation criteria for oncological PPs eects
are used so far.
Methods: A systematic literature review was conducted. Pubmed, Scopus,
Web of Science and Academic Search Elite were searched for (patient
pathway OR clinical pathway OR care pathway OR integrated pathway)
AND (evaluat* OR outcome* OR analysis OR assess*), ltering for oncol-
ogy. In total, 29 articles were included. e Leuven Clinical Pathway
Compass was used to categorize evaluation criteria.
Result: Almost all articles evaluated PPs in hospitals. Only one had an
inter-organizational PP scope. Most evaluation criteria are nancial (used
in 90% of the studies, e.g. length of stay, cost savings) and clinical crite-
ria (93%, e.g. complications, mortality, re-admission, clinical outcomes).
Process (45%, e.g. pathway variances, use of procedures) and service cri-
teria (45%, e.g. patient satisfaction, quality of life) were used less oen.
Team criteria occurred the least (17%, e.g. communication, professional
involvement). PPs for gastrointestinal cancers were evaluated most oen.
Discussion: Results show a lack of common evaluation standards for PPs
in cancer care. Criteria addressing key characteristics, i.e. network and
patient focus, are scarce. Further, the comparability of PP evaluation stud-
ies is limited due to undened and varying PP implementation status.
Conclusion: Criteria in use for oncological PP evaluation have limited
perspective and lack comprehensiveness to cover the complexity of PPs
in comprehensive cancer care. An evaluation framework including proce-
dural guidance and criteria also considering dierent PP implementation
levels would allow for PP benchmarking across comprehensive cancer
centers.
Disclosure Statement: e authors declare no conict of interest.
1039
S1 Guideline for prioritisation in gastrointestinal cancer care –
scarcity of ressources in the pandemic context
Anke Reinacher-Schick1; Pompiliu Piso2; Emmannouil Fokas3; Matthias
Ebert4; Tanja Zimmermann5; Ulrich Wedding6; Celine Lugnier1; Anna-Lena
Kraeft1; Olaf Schoer7; Sabine Sommerlatte8; Thomas Birkner9; Sarah
Förster10; Stefan Rolf Benz11; Monika Klinkhammer-Schalke12; Wolfgang
Knauf13; Ralf-Dieter Hofheinz14; Andrea Tannapfel10; Jochen Schmitt9;
Berhard Wörmann15,16; Jan Schildmann17
1Katholisches Klinikum Bochum, St. Josef Hospital Bochum, Ruhr Universität
Bochum, Mediznische Klinik V für Hämatologie und Onkologie mit
Palliativmedizin, Bochum
2Barmherzige Brueder Krankenhaus, Regensburg, Abteilung für Chirurgie,
Regensburg
3Goethe Universität Frankfurt , Universitätsklinikum Frankfurt, Klinik für
Strahlentherapie und Onkologie, Frankfurt
4Universitätsmedizin Mannheim, Medizinische Fakultät, Universität Heidelberg,
Medizinischen Klinik II. , Mannheim
5Medizinische Hochschule Hannover , Klinik für Psychosomatik und
Psychotherapie , Hannover
6Universitätsklinikum Jena, Klinik für Innere Medizin II , Abteilung
Palliativmedizin, Jena
7Zentrum für evidenzbasierte Gesundheitsversorgung, Universitätsklinikum und
Medizinische Fakultät Carl Gustav Carus an der Technischen Universität Dresden,
Dresden
8Institut für Geschichte und Ethik der Medizin, Medizinische Fakultät der Martin-
Luther Universität Halle-Wittenberg, Halle (Saale)
9Zentrum für evidenzbasierte Gesundheitsversorgung, Universitätsklinikum und
Medizinische Fakultät Carl Gustav Carus an der Technischen Universität Dresden,
Dresden
10Institut für Pathologie am Berufsgenossenschaftlichen Universitätsklinikum
Bergmannsheil, Ruhr-Universität Bochum, Bochum
11Krankenhaus Kliniken Böblingen , Klinik für Allgemein-, Viszeral- und
Kinderchirurgie, Böblingen
12Institut für Qualitätssicherung und Versorgungsforschung der Universität
Regensburg , Universität Regensburg , Regensburg
13Berufsverband der Niedergelassenen Hämatologen und Onkologen in
Deutschland e.V. , Köln
14Universitätsklinikum Mannheim, Mannheim Cancer Center, Mannheim
15DGHO Berlin, Deutsche Gesellschaft für Hämatologie und Onkologie e.V.,
Berlin
16Charité Berlin Virchow Campus, Universitätsklinikum Berlin, Medizinische
Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie, Berlin
17Instituts für Geschichte und Ethik der Medizin, Martin-Luther-Universität Halle-
Wittenberg, Halle (Saale)
Background: e COVID-19 pandemic has led to deviations in all sectors
of cancer care. We present multidisciplinarily approved recommendations
for ethically and empirically based prioritisation of procedures in times of
scarce resources for patients with colorectal and pancreatic cancer.
Methods: e CancerCOVID consortium conducted qualitative and
quantitative studies on ethical challenges and psychosocial stress of
patients and health care professionals in cancer care. For empirical analy-
ses we obtained data from AOK Plus, the main health insurance in Saxony,
AIO (Arbeitsgemeinscha internistische Onkologie) cancer centers, the
institute of Pathology Bochum, the ColoPredict Registry and data of
outpatient care from the BNHO (Berufsverband der Hämatologen und
Onkologen) and Onkotrakt AG. A selective literature review of interna-
tional data and guidelines focussing on the eects of the pandemic on
cancer care and allocation of resources was conducted. Structured group
discussions on justied criteria for prioritisation were held with experts
from oncology, ethics, law and health research. Recommendations for
prioritisation were formulated as S1 guideline with approval of 9 AWMF
Medical Societies, 22 multidisciplinary experts and patient representatives.
Results: e main principle for decisions on prioritisation in times of
scarce resources is the minimisation of individual and aggregated harm.
In case of relevant risk of harm from a possible low priority classication
or postponement prioritization decisions should be made individually for
the respective patients according to the multiple-eyes principle. Decision
making should involve dierent disciplines and professions depending
on local infrastructure. We concretised recommendations for 5 areas in
cancer care.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts138
Conclusion: Guidelines based on a broad multidisciplinary consensus
can give ethically and empirically based support in medical decision mak-
ing when resources are scarce. is can provide relief for decision-makers
and facilitate transparency and trust of patients and population.
Disclosure Statement: e authors declare no conict of interest.
1056
Financial distress of cancer patients in everyday counselling
of social services in Germany. A qualitative focus group study
Sophie Pauge1; Bastian Surmann1; Andrea Züger2; Luise Richter3;
Viktoria Mathies4; Thomas Ernst4; Wolfgang Greiner1; Natalja Menold3;
Eva Winkler2
1Universität Bielefeld, Fakultät für Gesundheitswissenschaften,
Gesundheitsökonomie und Gesundheitsmanagement, Bielefeld, Deutschland
2Universitätsklinikum Heidelberg, Nationales Centrum für Tumorerkrankungen
(NCT) Heidelberg, Sektion Translationale Medizinische Ethik, Heidelberg,
3Technische Universität Dresden, Institut für Soziologie, Professur für Methoden
der empirischen Sozialforschung, Dresden
4Universitätsklinikum Jena, Klinik für Innere Medizin II, Hämatologie und
Internistische Onkologie, Jena
Background: Financial distress (FD) has an eect on cancer patients
quality of life and distress [1]. For years, social services have recognized
an increasing need for counselling. A survey of social services identi-
ed a wide range of risk factors and a scattered picture of standardized
approaches to address patients at risk [2]. To better understand current
counselling practice and potential determinants of FD, a qualitative focus
group study with social services was performed.
Methods: A semi-structured focus group with n=4 social service repre-
sentatives from in- and outpatient centers in Germany was conducted. An
interview guideline was developed based on results of systematic reviews
on nancial toxicity [3, 4] and a survey of social services [2] . Transcripts
were analyzed using qualitative content analysis following Kuckartz.
Result: FD is discussed within rst consultations of social services by
default. Representatives recognized several risk factors, which can be clas-
sied into 7 categories: “Finance & work, “social environment, “housing”,
medical & treatment-related factors, “direct costs” and “individual per-
ception. e extent and type of approach to address FD varies and is usu-
ally based on personal experiences related to the risk factors. Standardized
screening tools are partly applied and most of them are neither validated
nor do they adequately address FD.
Discussion: Social services express the need for a standardized and prac-
tical screening tool. A validated German tool could support social services
in identifying patients at risk of experiencing FD. It might further support
the development of personalized and coordinated intervention schemes
to alleviate FD.
Conclusion: Financial distress plays an important role counselling and
the demand for coordinated guidance through social services will further
increase.
Literature:
1 Mehlis, K. et al., BMC Cancer, 2020
2 Surmann, B. et al., ZEFQ, 2021
3 Pauge, S.; Surmann, B et al., Cancers, 2021
4 Witte, J. et al. Ann. Oncol., 2019
Disclosure Statement: e authors declare the following: is research is funded
by Deutsche Krebshilfe.
Imaging
Poster
119
Augmented Reality (AR) Computed tomography (CT)-Guided
Liver Punctures: A Phantom Study Introducing A New Type Of
AR System
Vincent Van den Bosch1; Hizirwan Shukri Salim2; Njin-Zu Chen2;
Otto Stroosma2; Philipp Bruners1; Christiane Kuhl1; Peter Isfort1;
Federico Pedersoli1
1Universitätsklinikum Aachen, Klinik für Diagnostische und Interventionelle
Radiologie, Aachen, Deutschland
2Philips, Eindhoven, Niederlande
Background: To investigate the feasibility of a novel AR system using the
HoloLens 2 for performing CT-guided liver interventions.
Methods: A new kind of AR system was developed, oering projection
of CT-images and live optical tracking of the needle position as well as a
bull’s eye view as well as a visualization of the distance to the target. e
experiment was performed using a custom-made abdominal agar-agar
phantom, created from a segmented liver CT (3D Slicer) that contained
digitized target locations. ree radiologists with dierent levels of exper-
tise (resident, junior and senior sta member) performed the experiment,
consisting of 40 punctures. ereof 20 punctures were performed free-
hand and 20 punctures with AR-guidance. A CT-simulator soware was
used for the free hand punctures, sparing long CT-scanning times and so
allowing more punctures to be executed. Semi-structured interviews were
performed aer the experiment. For the statistical analysis, a two-tailed
Wilcoxon Signed-Rank test was performed.
Result: Duration of intervention was signicantly (p<0.05) improved in
all operators with a mean of 110,9 seconds in the free hand punctures and
38,7 seconds in the AR punctures (-65%). e mean accuracy was 4,7 mm
in the free hand group, while being 5,0 mm in the AR group (p>0.05). In
detail, the junior sta member had an improvement of accuracy of 1 mm
using AR (p<0.05), while the others showed no signicant improvement
regarding accuracy. All radiologists rated the AR-setup positively. In par-
ticular, the use of underlying CT imaging, a familiar method in everyday
clinical practice, was rated as advantageous.
Discussion: Like in existing literature, typical limitations of a preclini-
cal phantom study are present. Compared to other studies, a signicant
number of punctures in one experimental setting was performed, taking
advantage of the virtual CT setting.
Conclusion: is AR-system signicantly reduces intervention time and
has furthermore the potential to dramatically reduce the radiation burden
to the patient. ereby accuracy remains comparable.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 139
567
Longitudinal study on MRI and neuropathological ndings:
Neither DSC-perfusion derived rCBVmax nor vessel densities
correlate between newly diagnosed and progressive
glioblastoma
Eike Steidl1; Katharina Filipski2; Elke Hattingen1; Joachim P. Steinbach3;
Gabriele Maurer3
1Institut für Neuroradiologie, Universitätsklinikum Frankfurt
2Neurologisches Institut - Edinger Institut, Universitätsklinikum Frankfurt
3Dr. Senckenbergisches Institut für Neuroonkologie, Universitätsklinikum
Frankfurt
Purpose: When evaluating MRIs for glioblastoma progression, previous
scans are usually included into the review. Nowadays dynamic susceptibil-
ity contrast (DSC)-perfusion is an essential component in MR-diagnostics
of gliomas, since the extent of hyperperfusion upon rst diagnosis cor-
relates with gene expression and survival. We aimed to investigate if this
initial perfusion signature also characterizes the glioblastoma at time of
progression. If so, DSC-perfusion data from the initial diagnosis could be
of diagnostic benet in follow-up assessments.
Methods: We retrospectively identied 65 patients with isocitrate dehy-
drogenase wildtype glioblastoma who had received technically identical
DSC-perfusion measurements at initial diagnosis and at time of rst pro-
gression. We determined maximum relative cerebral blood volume values
(rCBVmax) by standardized re-evaluation of the data including leakage
correction. In addition, the corresponding tissue samples from 24 patients
were examined histologically for the maximum vessel density within the
tumor. Dierences (paired t-test/ Wilcoxon matched pairs test) and cor-
relations (Spearman) between the measurements at both timepoints were
calculated.
Results: e rCBVmax was consistently lower at time of progression com-
pared to rCBVmax at time of rst diagnosis (p<.001). ere was no cor-
relation between the rCBVmax values at both timepoints (r=.12). ese
ndings were reected in the histological examination, with a lower vessel
density in progressive glioblastoma (p=.01) and no correlation between
the two timepoints (r=-.07).
Conclusion: Our results suggest that the extent of hyperperfusion in glio-
blastoma at rst diagnosis is not a sustaining tumor characteristic. Hence,
the rCBVmax at initial diagnosis should be disregarded when reviewing
MRIs for glioblastoma progression.
Disclosure Statement: e authors declare no conict of interest.
873
Ultrasound guided biopsy of the mediastinum
Thorsten Nitsch; Julia Lanznaster; Preißler Sieglinde;
Elisabeth Neuwirth; Thomas Südho
Klinikum Passau, II. Med Klinik, Passau, Deutschland
Background: Mediastinal masses are oen an expression of an aggressive
disease. For this reason, rapid histology acquisition is important, since reli-
able histology forms the basis for further therapy planning. Sonography
is a widely available and gentle method that expands the possibilities of
rapid histology acquisition, but there is little data of sono.-guided biopsy
of the mediastinum. We report here on the eectiveness and complication
rate of this method.
Methods: is is a retrospective analysis of sono.-guided mediastinal
biopsies in our clinic. Ultrasound machine: Toshiba Aplio 400, later i800.
Depending on the location, the puncture was performed with a “convex
array” puncture probe or with a linear probe using the “freehand” tech-
nique. We used true-cut needles (16G to 18G) and a 10F drain. e biop-
sies were performed under local anesthesia and aseptic conditions. On
average, three biopsies and one cytology were performed. Complications
were classied into three grades: 1 for minor to 3 for severe complications.
Result: We performed 31 punctures of the mediastinum. e masses
ranged in size from 1.5 to 7.8 cm. In 27 cases (87%) a reliable histology
could be obtained, so that no further intervention was necessary. In two
cases, the histology could be obtained by sono-repuncture or CT-guided
puncture. In two cases the histology had to be claried by surgery. A com-
plication was recorded in only one case with slight pain. Histology results:
hm B-NHL:6, Adeno-NSCLC:5, SCLC:3, Hodgkin:3, hm T-NHL:2,
T-ALL:2, Squamous CUP:1, Anaplast SD-Ca:1, Mammaca :1, nm NHL:1,
abscess:1, thymoma:1, unspec:2
Conclusion: Base on our results we concluded that ultrasound-guided
biopsy of the mediastinum is a reliable and gentle method with a reliable
histology in 87% of the cases and slight complications (pain) in one case
(3%). Furthermore it is widely available and can therefore be used quickly
and in a time-saving manner. It can be performed on the bedside and in
an upright position in the oen highly symptomatic/dyspnoeic patients, it
is cost-eective and saves radiation.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts140
Leukemia, Myelodysplasia, and Transplantation
Best-of-Abstract-Vortrag
287
Survival outcomes from the QUAZAR AML-001 trial with
oral azacitidine (Oral-AZA) for patients with acute myeloid
leukemia (AML) in remission by disease subtype, cytogenetic
risk, and NPM1 mutation status at diagnosis (Dx)
Michael Pfeilstöcker1; Hartmut Döhner2; Andrew Wei3,4; Gail Roboz5,6;
Pau Montesinos7; Felicitas Thol8; Ignazia La Torre9; Barry Skikne10,11;
Wendy See-Zepeda10; Manuel Ugidos12; Alberto Risueño12; CL Beach10;
Daniel Menezes10
1Hanusch Hospital, Vienna, Österreich
2Universitätsklinikum Ulm, Ulm, Deutschland
3The Alfred Hospital, Melbourne, Australien
4Monash University, Melbourne, Australien
5Weill Cornell Medicine, New York, USA
6New York Presbyterian Hospital, New York, USA
7Hospital Universitari i Politècnic La Fe, Valencia, Spanien
8Medizinische Hochschule Hannover, Hannover, Deutschland
9Celgene, a Bristol-Myers Squibb Company, Boudry, Schweiz
10Bristol Myers Squibb, Princeton, USA
11University of Kansas Medical Center, Kansas City, USA
12BMS Center for Innovation and Translational Research Europe (CITRE), a Bristol-
Myers Squibb Company, Seville, Spanien
Background: In the phase 3 QUAZAR AML-001 trial, Oral-AZA main-
tenance therapy signicantly improved overall and relapse-free survival
(OS/RFS) vs placebo (PBO) in older patients (pts) in remission (median
[med] 24.7 vs 14.8 mo; P<0.001). We assessed OS/RFS in QUAZAR AML-
001 pt subgroups dened by AML subtype (de novo/secondary), cytoge-
netic risk (intermediate [int] or poor), and NPM1/FLT3 mutational status
at Dx.
Methods: Within 4 mo of achieving rst CR/CRi, pts were randomized to
Oral-AZA 300 mg or PBO x14d/28d cycles. Measurable residual disease
(MRD) was assessed at screening (cuto ≥0.1%).
Result: In 429/472 pts (91%) with de novo AML, Oral-AZA signicantly
increased OS vs PBO (med 23.2 vs 14.6 mo; hazard ratio [HR] 0.73;
P=0.007) and RFS (10.2 vs 4.9 mo; HR 0.66; P<0.001). ere was a trend
for better OS in pts with secondary AML (n=43) with Oral-AZA (28.2 vs
15.7 mo; HR 0.58; P=0.11) and signicantly longer RFS (4.7 vs 2.4 mo;
HR 0.47; P=0.012). For pts with int-risk cytogenetics (86%), OS was sig-
nicantly better with Oral-AZA (25.4 vs 15.9 mo; HR 0.73; P=0.009), as
was RFS (11.0 vs 5.8 mo; HR 0.66; P<0.001). In poor-risk pts (14%) there
were trends for better OS with Oral-AZA vs PBO (13.9 vs 7.4 mo; HR
0.61; P=0.06), and RFS (4.6 vs 3.7 mo; HR 0.63; P=0.08). At Dx, 29.2%
(137/469) had NPM1mut, 9.8% (48) had FLT3-ITD, and 6% (30) had
NPM1mut and FLT3-ITD. In the PBO arm, NPM1mut vs NPM1wt was prog-
nostically favorable for RFS (6.9 vs 4.6 mo; HR 0.64; P=0.008) with a trend
for better OS (15.9 vs 14.6 mo; HR 0.75; P=0.10). Med OS for NPM1mut
pts was much longer with Oral-AZA vs PBO (46.1 vs 15.9 mo; HR 0.57;
P=0.014), as was RFS (23.2 vs 6.9 mo; HR 0.55; P=0.001). More pts with
NPM1mut were MRD– (61.7%) vs MRD+ (38.4%) at screening (P=0.018).
In NPM1wt pts, Oral-AZA signicantly increased OS (19.6 vs 14.6 mo; HR
0.77; P=0.036) and RFS (7.7 vs 4.6 mo; HR 0.69; P=0.003).
Discussion: Oral-AZA signicantly improved OS/RFS for pts with de
novo AML and int-risk cytogenetics. Pts with NPM1mut had an OS benet
of >2.5 yrs vs PBO.
Conclusion: NPM1mut is prognostically favorable and predictive of
increased OS with Oral-AZA.
Disclosure Statement: e authors declare the following: MP reports honoraria
for speaker services and consultancy for Abbvie, Astellas, BMS, Jazz, Novartis, and
Takeda; research funding: BMS.
Poster
12
Bone marrow derived stromal cells from Myelodysplastic
Syndromes are altered but not clonally mutated in vivo
Johann-Christoph Jann1; Eva Altrock1; Nanni Schmitt1; Vladimir Ryabov1;
Qingyu Xu1; Ali Darwich1; Georgia Metzergoth1; Wolf-Karsten Hofmann1;
Daniel Nowak1
1Universitätsmedizin Mannheim, III. Medizinische Klinik, Mannheim
Purpose: Increasing evidence suggests that the pathogenesis of
Myelodysplastic Syndromes (MDS) is not only driven by the hematopoi-
etic compartment but also the bone marrow (BM) microenvironment.
Seminal studies in murine models have demonstrated that isolated muta-
tions in the BM niche can disrupt the non-mutated hematopoietic com-
partment and induce MDS-like diseases. An unanswered question has
therefore been whether primary MDS in humans is possibly also associ-
ated with acquired mutations in the BM stroma.
Methods: In order to address this hypothesis, we performed a compre-
hensive whole exome sequencing study on BM derived in vitro expanded
mesenchymal stromal cells (MSCs) of n=98 MDS and myeloid neopla-
sia patients and a control group of n=20 healthy individuals. In addition,
MSCs in serial culture passages and dierent BM aspirations from the
same patients were sequenced in order to investigate whether acquired
mutations in MSCs were artefacts of the ex vivo expansion. Putatively high
condence mutations were further backtracked by deep re-sequencing in
primary sorted CD45-CD235a-CD31-CD271+ BM cells in n=9 cases.
Results: We discovered multiple recurrently acquired mutations in
expanded MSCs of MDS patients in genes such as ZFX (n=8/98), RANK
(n=5/98), and others. Expanded MSCs from MDS patients displayed a
higher mutational burden and distinct mutational signatures. However, all
validation experiments in serial cultures and primary sorted MSCs indi-
cated that the discovered mutations were expanded by in vitro culture but
not present in relevant cell populations in the primary BM.
Conclusion: us, we conclude that there is no evidence for clonal muta-
tions in the BM stroma of MDS patients.
Disclosure Statement: e authors declare no conict of interest.
268
Late toxicities after total-body irradiation – a long-term
analysis of hematological patients
Michael Oertel1; Jonas Martel1; Jan-Henrik Mikesch2; Matthias Stelljes2;
Hans Theodor Eich1
1Klinik für Strahlentherapie - Radioonkologie, Universitätsklinikum Münster,
Münster, Deutschland
2Knochenmarktransplantationszentrum, Universitätsklinikum Münster, Münster,
Deutschland
Background: Total-body irradiation (TBI) enables an eective myeloab-
lative conditioning before allogeneic stem cell transplantation. With the
whole body being the radiation target, various toxicities may arise, which
prompted us to investigate long-term sequelae of this treatment concept
in a large patient cohort [1]
but is accompanied by relevant (long-term.
Methods: An institutional retrospective search identied 322 patients
with acute leukemia or myelodysplastic syndrome with a minimum fol-
low-up of one year (median 68 months). Median age at transplantation
was 47 years and TBI was done with 8 Gy (236 patients) or 12 Gy (82
patients) in most cases.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 141
Results: Pulmonary, cardiac, ocular, neurological and renal toxicities
were reported in 23.9 %, 14.3 %, 23.6 %, 23.9 % and 20.2 % of all patients,
respectively. Most of these side eects were grade 1-2 (64.9 % - 89.2 %) for
the respective categories. e use of 12 Gy TBI was associated with a sig-
nicant increase in ocular toxicities (p=0.013) and in severe mucositis (p
< 0.001). In addition, chronic gra versus host disease was accompanied
by a shortened pulmonary-toxicity free interval (133.0 months (chronic)
vs. 144.9 months (acute) vs. 183.2 months (none); p<0.001) and by an
increase in ocular toxicity (relative risk 5.88; p<0.001).
Discussion: Although diverse toxicities were observed, the majority was
mild to moderate. An increased TBI dose, in balance with an adapted che-
motherapy regimen, does not lead to a disproportional rise in side eects,
with ocular toxicities and mucositis being the only toxicities increased in
the 12 Gy group.
Conclusion: Total-body irradiation bears a diverse but manageable toxic-
ity prole. Long term follow-up is mandatory for a complete evaluation of
the resulting side eects.
Indication of source:
1. Oertel M et al (2021) Cancers 13:2946. https://doi.org/10.3390/can-
cers13122946
Disclosure Statement: e authors declare no conict of interest.
A preliminary analysis has been presented at the 27th Annual Meeting of the
German Society of Radiation Oncology. Data on pulmonary toxicities were
published before [1].
281
Luspatercept Reduces Red Blood Cell Transfusions (RBCT) in
Patients with Lower-Risk Myelodysplastic Syndromes (LR-
MDS) Regardless of Baseline Transfusion Burden (TB) in the
MEDALIST Study
Uwe Platzbecker1; Guillermo Garcia-Manero2; Pierre Fenaux3;
Rena Buckstein4; Valeria Santini5; Maria Diez-Campelo6; Derek Tang7;
Rodrigo Ito8; Shannon Fabre7; Emily Mantovani8; Roberto Zooli9;
Dimana Miteva7; Christina Hughes7; Wasiulla Khan8; Rami S. Komrokji10;
Ulrich Germing11
1University Hospital Leipzig, Medical Clinic and Policlinic 1, Hematology and
Cellular Therapy, Leipzig, Deutschland
2The University of Texas MD Anderson Cancer Center, Department of Leukemia,
Houston, USA
3Université Paris 7, Service dHématologie Séniors, Hôpital Saint-Louis, Paris,
Frankreich
4Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, Kanada
5University of Florence, MDS Unit, Azienda Ospedaliero Universitaria Careggi,
Florence, Italien
6University Hospital of Salamanca, Hematology Department, Institute of
Biomedical Research of Salamanca, Salamanca, Spanien
7Bristol Myers Squibb, Princeton, USA
8Formerly Bristol Myers Squibb, Princeton, USA
9Bristol Myers Squibb, Braine-lAlleud, Belgien
10Mott Cancer Center, Tampa, USA
11University Hospital of Düsseldorf, Düsseldorf, Deutschland
Background: MEDALIST (NCT02631070) is a randomized, phase 3
trial to assess the ecacy and safety of luspatercept in patients (pts) with
anemia due to LR-MDS with ring sideroblasts. Luspatercept reduced red
blood cell TB, with signicant rates of transfusion independence (Fenaux
et al. NEJM 2020;382:140–51). Using data from MEDALIST we assess the
eect of luspatercept on cumulative RBCT units and visits in LR-MDS pts
according to their baseline TB levels.
Methods: Eligible pts were refractory, intolerant, or unlikely to respond
to erythropoiesis-stimulating agents, and required regular RBCT (≥ 2
units/8 weeks [wks]) in the 16 wks prior to randomization. Overall, 229
pts were randomized 2:1 to receive either luspatercept (n = 153) or pla-
cebo (n = 76) every 3 wks through to clinical assessment visit at Wk 25
(data cuto: July 1, 2019). Mean cumulative RBCT units and visits were
estimated. Luspatercept responders were dened as pts achieving RBC-TI
≥ 8 wks during Wks 1–24; low TB (LTB) pts received < 6 RBCT units/8
wks and high TB (HTB) pts received ≥ 6 RBCT units/8 wks at baseline.
Result: LTB and HTB pt numbers were comparable in the luspatercept
and placebo arm at baseline; 87/153 (56.9%) in luspatercept vs 43/76
(56.6%) in placebo were LTB, whereas 66/153 (43.1%) vs 33/76 (43.4%)
were HTB. Mean cumulative RBCT units received (95% condence inter-
val [CI]) in LTB pts were 6.8 (5.6–8.4) in the luspatercept arm (n = 81/87)
vs 13.2 (11.5–15.2) in placebo (n = 38/43); and for HTB pts, were 17.2
(15.1–19.6) in the luspatercept group (n = 47/66) vs 24.2 (21.3–27.4) in
placebo (n = 30/33). Mean cumulative RBCT visits (95% CI) in LTB pts
were 4.0 (3.3–4.8) in the luspatercept arm (n = 81/87) vs 7.2 (6.3–8.3) in
placebo (n = 38/43); and for HTB pts were 9.4 (8.3–10.7) in the luspater-
cept arm (n = 47/66) vs 12.5 (11.0–14.2) in placebo (n = 30/33).
Conclusion: In MEDALIST, luspatercept reduced RBCT units and visits
relative to placebo over the rst 24-wk period in pts with LR-MDS regard-
less of their baseline TB. is abstract was presented at EHA 2021 (Garcia-
Manero et al. HemaSphere 2021;5[S2]:EP920).
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
282
Benet of Continuing Luspatercept Therapy in Patients with
Lower-Risk Myelodysplastic Syndromes (LR-MDS) Who Did
Not Achieve Red Blood Cell Transfusion Independence (RBC-
TI) by Week 25 in the MEDALIST Study
Uwe Platzbecker1; Ulrich Germing2; Pierre Fenaux3; Rena Buckstein4;
Valeria Santini5; Maria Diez-Campelo6; Derek Tang7; Rodrigo Ito8;
Shannon Fabre7; Emily Mantovani8; George Zhang7; Xianwei Ha7;
Dimana Miteva7; Christina Hughes7; Wasiulla Khan8; Rami S. Komrokji9;
Guillermo Garcia-Manero10
1University Hospital Leipzig, Medical Clinic and Policlinic 1, Hematology and
Cellular Therapy, Leipzig, Deutschland
2University Hospital of Düsseldorf, Düsseldorf, Deutschland
3Université Paris 7, Service dHématologie Séniors, Hôpital Saint-Louis, Paris,
Frankreich
4Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, Kanada
5University of Florence, MDS Unit, Azienda Ospedaliero Universitaria Careggi,
Florence, Italien
6University Hospital of Salamanca, Hematology Department, Institute of
Biomedical Research of Salamanca, Salamanca, Spanien
7Bristol Myers Squibb, Princeton, USA
8Formerly Bristol Myers Squibb, Princeton, USA
9Mott Cancer Center, Tampa, USA
10The University of Texas MD Anderson Cancer Center, Department of Leukemia,
Houston, USA
Background: MEDALIST (NCT02631070) is a randomized, place-
bo-controlled phase 3 trial to assess the ecacy and safety of luspatercept
in patients (pts) with anemia due to LR-MDS with ring sideroblasts. e
primary endpoint was RBC-TI ≥ 8 weeks (wks) during Wks 1–24 (Fenaux
et al. NEJM 2020;382:140–51). Here we assess the clinical benet of con-
tinued luspatercept treatment for pts who did not achieve the primary
endpoint in the MEDALIST trial.
Methods: Eligible pts were refractory, intolerant, or unlikely to respond
to erythropoiesis-stimulating agents and required regular RBC transfu-
sions (≥ 2 units/8 wks) in the 16 wks pre-randomization. Pts were ran-
domized 2:1 to receive luspatercept (n = 153) or placebo (n = 76) every
3 wks to clinical assessment at Wk 25. is analysis includes pts who did
not achieve the primary endpoint on luspatercept but continued treat-
ment (data cuto: July 1, 2019). Every 24 wks, transfusion burden (TB),
serum ferritin (SF) levels, and hematologic improvement-erythroid (HI-
E) response (dened as ≥ 4 units/8 wks decrease in RBC transfusions [≥ 4
RBC units/8 wks baseline TB] or ≥ 1.5 g/dL increase in hemoglobin/8 wk
[< 4 RBC units/8 wks baseline TB]) were assessed.
Result: Of 68 pts who did not achieve the primary endpoint, 11 (16.2%)
achieved RBC-TI ≥ 8 wks in Wks 25–48; 36 experienced a mean decrease
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts142
of 1.3 RBC units transfused vs baseline. 30/68 (44.1%) pts achieved SF
reduction vs baseline in Wks 25–48, and 7/39 (17.9%) shied from ≥ 1,000
µg/L SF level at baseline to < 1,000 µg/L. In Wks 1–48, 41/68 (60.3%) pts
achieved ≥ 50% RBC TB reduction vs baseline for ≥ 8 wks; 32/68 (47.1%)
pts achieved HI-E. By data cuto, 41/68 (60.3%) pts achieved ≥ 50%
reduction in TB vs baseline for ≥ 8 wks, 15/68 (22.1%) achieved RBC-TI ≥
8 wks, and 33/68 (48.5%) achieved HI-E.
Conclusion: A range of clinical improvements, including reduced TB
and SF, and TI, were achieved by a considerable proportion of pts in the
MEDALIST study who did not achieve the primary endpoint, but con-
tinued to receive luspatercept. is abstract was presented at EHA 2021
(Germing et al. HemaSphere 2021;5[S2]:EP915).
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
323
Histone demethylase KDM4C prevents cellular senescence in
JAK2-mutated neoplasms
Philipp Ernst1,2; Laura Kirchner3; Tina. M. Schnöder3; Nicolas Huber3;
Florian Perner4; Theresa Eifert3; Chen-Jen Hsu3; Nuria Tubío-Santamaría3;
Martin Ungelenk5; Christian A. Hübner5; Astrid Tannert6;
Joachim H. Clement1; Andreas Hochhaus1; Florian H. Heidel3,7
1Universitätsklinikum Jena, Innere Medizin 2, Hämatologie und Onkologie, Jena,
Deutschland
2Universitätsklinikum Jena, ForschungsprogrammElse Kröner-
Forschungskolleg AntiAge“, Jena, Deutschland
3Universitätsmedizin Greifswald, Innere Medizin 2, Hämatologie, Onkologie,
Stammzelltransplantation und Palliativmedizin, Greifswald, Deutschland
4Dana-Farber Cancer Institute, Department of Pediatric Oncology, Harvard
University, Boston, USA
5Universitätsklinikum Jena, Institut für Humangenetik, Jena, Deutschland
6Leibniz-Institut für Photonische Technologien, Labor für Biophotonik und
Bildgebung, Jena, Deutschland
7Fritz-Lipmann-Institut, Leibniz-Institut für Altersforschung, Jena, Deutschland
Background: JAK2 V617F mutations are associated with myeloprolifer-
ative neoplasms (MPN). Current therapeutic options are ineective to
eradicate JAK2-mutated clones. Hence, MPN patients are at risk of pro-
gressing to secondary acute myeloid leukemia. We sought to determine
genetic vulnerabilities that may prevent persistence and progression of
JAK2-mutated clones.
Methods: Genome-scale lentiviral CRISPR-Cas9 screen. Proliferation
and cell growth competition assay. Transcriptome analysis using RNA-
sequencing. Senescence screen using SA-ßGal assay, laser scanning
microscopy and Western blot. In vivo KDM4C CRISPR-Cas9 knockout
using NXG Mouse Xenogra.
Result: Using genome-scale CRISPR-Cas9 screen KDM4C showed depen-
dence in HEL cells irrespective of co-treatment with Ruxolitinib. Genetic
deletion of KDM4C in human and murine JAK2-mutated cells led to sig-
nicant loss of proliferative advantage compared to non-deleted controls.
Transcriptome analyses on HEL cells following KDM4C-deletion showed
signicant deregulation of senescence associated genes. GSEA revealed
also enriched PI3K/AKT/mTOR and NF-κB signaling. A signicant
increase in SA-ßGal and p21 expression was detected. NXG mice with
JAK2-mutated leukemia and KDM4C-KO showed signicantly improved
survival compared to non-targeting controls.
Discussion: Upon treatment with Ruxolitinib, JAK2-mutated cells sur-
vived depending on KDM4C expression. In vivo models of AML have
shown delayed disease development following deletion of KDM4C. e
evasion of senescence by KDM4C in JAK2-mutated cells observed here
has been described so far in melanocytic cells, and its loss was also associ-
ated with loss of H3K9me3.
Conclusion: JAK2-mutated cells are dependent on KDM4C activity irre-
spective to JAK-inhibitor treatment. Inhibition of KDM4C results in a
proliferative disadvantage of JAK2-mutant cells, which can be explained
by induction of cellular senescence. Sequential therapy combining
KDM4C inactivation and senolysis may represent a promising therapeutic
approach for JAK2-mutated MPN.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
374
First Interim Analysis Of ALPINE Study: Results Of A Phase 3
Randomized Study Of Zanubrutinib Vs Ibrutinib In Patients
With Relapsed / Refractory Chronic Lymphocytic Leukemia /
Small Lymphocytic Lymphoma (CLL / SLL)
Peter Hillmen1; Barbara Eichhorst2; Jennifer R. Brown3; Nicole Lamanna4;
Susan O’brien5; Constantine S. Tam6,7,8,9; Lugui Qiu10; Maciej Kazmierczak11;
Keshu Zhou12; Martin Šimkovič13,14; Jiri Mayer15; Amanda Gillespie-
Twardy16; Mazyar Shadman17,18; Alessandra Ferrajoli19; Peter S. Ganly20;
Robert Weinkove21,22; Tommi Salmi23; Meng Ji24; Jessica Yecies23;
Kenneth Wu24; William Novotny23; Jane Huang23; Wojciech Jurczak25
1St Jamess University Hospital, Leeds, Vereinigtes Königreich
2Universität zu Köln, Center for Integrated Oncology, Köln, Deutschland
3Dana-Farber Cancer Institute, Department of Medical Oncology, Boston, USA
4The Herbert Irving Comprehensive Cancer Center, Columbia University, New
York, USA
5The Chao Family Comprehensive Cancer Center, University of California,
Orange, USA
6Peter MacCallum Cancer Centre, Melbourne, Australien
7Universität Melbourne, Parkville, Australien
8St. Vincents Hospital Melbourne, Fitzroy, Australien
9Royal Melbourne Hospital, Parkville, Australien
10Chinese Academy of Medical Sciences, Peking Union Medical College, Tianjin,
China, VR
11Karol-Marcinkowski-Medizinische-Universität Posen, Department of
Hematology and Bone Marrow Transplantation, Poznań, Polen
12Aliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital,
Zhengzhou, China, VR
13Fakultní nemocnice Hradec Králové, 4th Department of Internal Medicine -
Hematology, Hradec Králové, Tschechische Republik
14Karls-Universität, Faculty of Medicine, Prague, Tschechische Republik
15Masaryk-Universität, University Hospital, Department of Internal Medicine-
Hematology and Oncology, Brno, Tschechische Republik
16Blue Ridge Cancer Care - Roanoke, Roanoke, USA
17Fred Hutchinson Cancer Research Center, Seattle, USA
18Universität von Washington, Department of Medicine, Seattle, USA
19University of Texas MD Anderson Cancer Center, Department of Leukemia,
Houston, USA
20Christchurch Hospital , Department of Haematology, Christchurch, Neuseeland
21Wellington Blood and Cancer Centre, Capital & Coast District Health Board,
Wellington, Neuseeland
22Cancer Immunotherapy Programme, Malaghan Institute of Medical Research,
Wellington, Neuseeland
23BeiGene USA, Inc., San Mateo, USA
24BeiGene (Beijing) Co., Ltd., Beijing, China, VR
25Maria Skłodowska-Curie Institute of Oncology, Krakow, Polen
e increased specicity of zanubrutinib (zanu) was hypothesized to min-
imize toxicities related to ibrutinib (ibr) o-target inhibition, and more
complete and sustained BTK occupancy by zanu may improve ecacy
outcomes. Activity and tolerability of zanu in patients (pts) with CLL/SLL
has been demonstrated in early phase CLL/SLL trials. ALPINE (BGB-
3111-305; NCT03734016) is a global, randomized, phase 3 study compar-
ing zanu vs ibr in pts with relapsed/refractory (R/R) CLL/SLL. We present
results of a preplanned interim analysis of the ALPINE study scheduled
~12 months aer the rst 415 pts were enrolled.
Patients were randomly assigned 1:1 to receive zanu 160 mg BID or ibr
420 mg QD until disease progression. Randomization was stratied by age
(<65 years vs ≥65 years), geographic region, refractory status, and del17p/
TP53 mutation status. e primary endpoint was ORR per investigator,
using 2008 iwCLL guidelines and Lugano criteria for SLL.
Between 1 Nov 2018 and 20 Dec 2019, 415 pts were randomized. At a
median follow-up of 15 months, ORR was signicantly higher with zanu
vs ibr (78.3% vs 62.5%, 2-sided P=0.0006). ORR was higher in pts with
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 143
del11q (83.6% vs 69.1%) and del17p (83.3% vs 53.8%) with zanu, as were
overall 12-month PFS (94.9% vs 84.0%) and OS rates (97.0% vs 92.7%).
e rate of atrial brillation/utter was signicantly lower with zanu (2.5%
vs 10.1%, 2-sided P=0.0014). Rates of major bleeding (2.9% vs 3.9%) and
adverse events leading to discontinuation (7.8% vs 13.0%) or death (3.9%
vs 5.8%) were also lower with zanu. Neutropenia was more common with
zanu (28.4% vs 21.7%); while grade ≥3 infections were lower with zanu
(12.7% vs 17.9%).
In this interim analysis, zanu had a superior response rate, improved
OS and PFS, and a lower rate of atrial brillation/utter vs ibr in pts with
R/R CLL/SLL.
e ALPINE study met its primary endpoint and conrmed that with
more complete and sustained BTK occupancy and more selective BTK
inhibition than ibr, zanu results in improved ecacy and safety outcomes
in pts with R/R CLL/SLL.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
956
Preliminary Safety and Ecacy Of BGB-11417, a Potent and
Selective B-Cell Lymphoma 2 (BCL2) Inhibitor, in Patients (Pts)
with Acute Myeloid Leukemia (AML)
Jake Shortt1; Uwe Platzbecker2; Shuh Ying Tan3; Paul Cannell4;
Teng Fong Ng5; Chun Yew Fong6; Sundra Ramanathan7; Rajeev
Rajagopal8; Sophie Leitch9; Robin Gasiorowski10; Carolyn Grove11;
Douglas Lenton12; Peter Tan13; Courtney Dinardo14; Ming Tat Ling15; Si
Cheng15; Yuan Liu15; Melannie Co15; Wai Y. Chan15; David Simpson15;
Andrew H. Wei13,16
1Monash University and Monash Health, School of Clinical Sciences, Clayton,
Australien
2Leipzig University Hospital, Leipzig, Deutschland
3St Vincents Hospital Melbourne, Fitzroy, Australien
4Fiona Stanley Hospital, Murdoch, Australien
5Gold Coast University Hospital, Southport, Australien
6Austin Health, Heidelberg, Australien
7The Saint George Hospital-Kogarah, Kogarah, Australien
8Middlemore Hospital, Auckland, Neuseeland
9North Shore Hospital, Auckland, Neuseeland
10Concord Repatriation General Hospital, Concord West, Australien
11Linear Clinical Research & Sir Charles Gairdner Hospital, Nedlands, Australien
12Orange Health Service (Central West Cancer Care Centre), Orange, Australien
13One Clinical Research, Nedlands, Australien
14University of Texas MD Anderson Cancer Center, Houston, USA
15China and BeiGene USA, Inc., San Mateo, USA
16Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Department of
Clinical Haematology, Melbourne, Australien
Background: BCL2, a key apoptosis regulator, is aberrantly expressed
in many hematologic malignancies. e highly selective BCL2 inhibitor,
BGB-11417, demonstrated more potent antitumor activity than vene-
toclax in preclinical studies. Here, preliminary results for BGB-11417 +
azacitidine (aza) in AML are presented.
Methods: BGB-11417-103 (NCT04771130) is an ongoing, phase 1b/2,
global, dose-escalation/expansion study. Eligible pts have treatment
(tx)-naïve (TN) AML (unt for intensive induction chemotherapy) or
relapsed/refractory (R/R) AML (no prior aza or BCL2 inhibitors). Pts
received 40mg (Cohort 1), 80mg (Cohort 2), or 160mg (Cohort 3) BGB-
11417 for 10 d + aza (75 mg/m2 x 7 d). Cycle 1 had a 4-d BGB-11417
ramp-up. Dose-limiting toxicity (DLT) through Day 28 (nonhemato-
logic) and Day 42 (hematologic), tx-emergent AEs, and responses (2017
European LeukemiaNet criteria) were assessed.
Result: As of 10 Jan2022, 27 pts were treated (Cohort 1 n=6; Cohort 2
n=15; Cohort 3 n=6). Median age was 80 y (TN n=18) and 70 y (R/R n=9);
44% had adverse karyotype. At a median follow-up of 2.1 mo and median
tx duration of 1.8 mo (range 0.3-7.6), 2/23 evaluable pts had DLTs: Grade
[Gr]4 neutropenia and Gr4 thrombocytopenia (Cohort 2) which did not
meet safety stopping criteria. 1 pt (Cohort 3) with chronic kidney disease
had asymptomatic laboratory tumor lysis syndrome. e most common
nonhematologic AEs were constipation (37%) and aza injection-site reac-
tion (33%). e most common Gr≥3 hematologic AEs were neutropenia
(44%), thrombocytopenia (41%), and anemia (37%). No pts had BGB-
11417 dose reductions. 10 pts discontinued tx: AEs (n=3), proceeding to
transplant (n=3), withdrawal (n=2), or disease progression (n=2). CR/
CRh rates were 56% (TN) and 44% (R/R). 7/9 CRs occurred by the end
of Cycle 1.
Discussion: Preliminary data suggest that 10-d BGB-11417 + aza was
well-tolerated with promising activity in AML. Most AEs were low-grade
in severity. 2 DLTs were seen across the 3 dose levels tested.
Conclusion: BGB-11417 + aza resulted in a majority of CR by the end of
Cycle 1 and was well-tolerated in AML.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
1042
The signicance of BCR-ABL dependent EpCAM expression for
treatment resistance in CML
Tara Towhidi1; Ruimeng Zhuang2; Manfred Jücker2; Vijay Kumar Boddu1;
Oliver Gires3; Hauke Busch4; Lena Illert5; Justus Duyster5; Timo Gemoll6;
Frank Gieseler1; Nikolas von Bubno1; Sivahari Prasad Gorantla1
1Klinik für Hämatologie und Onkologie, UKSH, Lübeck, Deutschland
2Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland,
3Ludwig-Maximilians-Universität München, München, Deutschland,
4Institut für experimentelle Dermatologie, UKSH, Lübeck, Deutschland,
5Uniklinik Freiburg , Freiburg im Breisgau, Deutschland,
6Klinik für Chirurgie, UKSH, Lübeck, Deutschland
Background: Although tyrosine kinase inhibitors (TKIs) show a remark-
able clinical response against BCR-ABL mediated chronic myeloid leu-
kemia (CML) 15% of the patients develop a resistance. One of the main
reasons for the failure of TKIs is the protection of leukemic stem cells
(LSCs) in the bone marrow. Understanding the complex signaling mech-
anisms which play a major role in in the protection of LSCs is required to
develop more ecient therapies. With this aim we focused on the role of
cell adhesion molecules playing a major role in CML stem cell interaction
with stromal cells.
Methods: Western Blot, qPCR and FACS were used to identify levels of
cell surface markers in 22 leukemia cell lines. Imatinib and nilotinib were
used to treat cells. A knockdown model was used to determine the func-
tional role of EpCAM in K562 cells.
Result: Analysis of 22 cell lines for the cell surface molecules EpCAM,
CD147 and CD47 demonstrated that BCR-ABL positive CML cells show
a signicantly higher expression of EpCAM. Treatment of K562 and Lama
84 cells with TKIs lead to downregulation of EpCAM expression, while
the TKI resistant T315I variant failed to downregulate EpCAM. In addi-
tion, only K562 and Lama 84 cell displayed the activation of ß-catenin
compared to other leukemia cell lines. We observed EpCAM being pro-
cessed and generating EpICD only in BCR-ABL+ cell lines. Overexpression
of EpCAM and EpICD in K562 cells lead to a strong activation of the
MAPK pathway and enhanced TKI resistance. Finally, downregulation of
EpCAM in K562 cells lead to a decrease in cell proliferation followed by
downregulation ofc-myc andCyclin D.
Discussion: Our results suggest that EpCAM expression is BCR-ABL
Kinase mediated. EpCAM knockdown leads to enhanced sensitivity
against TKIs. Our ongoing in vivo mouse model and gene expression
based functional studies will further delineate the role of EpCAM in the
pathogenesis of CML.
Conclusion: Dual inhibition of BCR-ABL and EpCAM mediated cell sig-
naling might be benecial for CML patients. e role of EpCAM in BCR-
ABL+ CML requires further research.
Reference:
e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts144
Lung Cancer
Best-of-Abstract-Vortrag
817
Comprehensive Proling of Tumor Heterogeneity and Its
Microenvironment in Advanced Non-small Cell Lung Cancer at
Single Cell Resolution
Reinhard Buettner1; Yuanyuan Chen2; Margarete Odenthal1; Nan Fang2;
Caicun Zhou3
1Uniklinik Köln, Köln, Deutschland
2Singleron Biotechnologies, Köln, Deutschland
3Tongji University School of Medicine-Shanghai Pulmonary Medicine Hospital,
Shanghai, China, VR
Background: Lung cancer is a highly heterogeneous disease. Cancer cells
and cells within the tumor microenvironment together determine disease
progression, as well as response to or escape from treatment.
Methods: To map the cell type-specic transcriptome landscape of cancer
cells and their tumor microenvironment in advanced non-small cell lung
cancer (NSCLC), we analyzed 42 tissue biopsy samples from stage III/IV
NSCLC patients by single cell RNA sequencing and presented the large
scale, single cell resolution proles of advanced NSCLCs.
Result: In addition to cell types described in previous single cell studies
of early stage lung cancer, we were able to identify new cell types such
as follicular dendritic cells and T helper 17 cells. Tumors from dierent
patients display large heterogeneity in cellular composition, chromosomal
structure, developmental trajectory, intercellular signaling network and
phenotype dominance.
Discussion: Our study revealed a correlation of tumor heterogeneity with
tumor associated neutrophils, which might help to shed light on their
function in NSCLC.
Conclusion: We were able to analyze 42 biopsies from late-stage NSCLC
patients for scRNAseq, and identied for the rst time the tumor hetero-
geneity and immune microenvironment signatures of late stage NSCLC
patients.
Disclosure Statement: e authors declare no conict of interest.
911
Durvalumab (D) + platinum-etoposide (EP) in 1L extensive-
stage small-cell lung cancer (ES-SCLC): Exploratory analysis of
SCLC molecular subtypes in CASPIAN
Mingchao Xie1; Priti Chugh1; Helen Broadhurst2; Zhongwu Lai1; David
Whitston1; Luis Paz-Ares3; Carl Gay4; Lauren Byers4; Charles M. Rudin5; Ross
Stewart6; J. Carl Barrett1; Yashaswi Shrestha7; Jens Panse8
1AstraZeneca, Waltham, USA
2Plus-Project Ltd, Alderley Park, Vereinigtes Königreich
3Hospital Universitario 12 de Octubre, Madrid, Spanien
4The University of Texas MD Anderson Cancer Center, Houston, USA
5Memorial Sloan Kettering Cancer Center, New York, USA
6AstraZeneca, Cambridge, Vereinigtes Königreich
7AstraZeneca, Gaithersburg, USA
8University Hospital RWTH Aachen, Aachen, Deutschland
Background: In the CASPIAN study 1L D+EP signicantly improved OS
vs EP in pts with ES-SCLC with benet sustained aer >3 years of median
follow-up (HR 0.71; 95% CI 0.60-0.86; p=0.0003; median OS [mOS] 12.9
vs 10.5 mos). 4 SCLC subtypes with distinct therapeutic vulnerabilities
were identied using 2 methods (Rudin et al, 2019; Gay et al, 2021) based
on dierential gene expression. In this exploratory analysis using RNA
sequencing (RNAseq) data from CASPIAN we explored the concordance
between the 2 methods and the association of subtypes with OS.
Methods: Pts with ES-SCLC received 4 cycles of D+EP followed by main-
tenance D or up to 6 cycles of EP. RNAseq data were generated from FFPE
tumor samples collected at screening. Data cuto: Mar 22, 2021.
Results: 57/268 (21.3%) pts in the D+EP arm and 47/269 (17.5%) pts in
the EP arm had RNAseq data (biomarker-evaluable population; BEP). In
BEP the % of pts with WHO PS 1 was slightly higher and the % with
brain metastases slightly lower at baseline vs the ITT population. In BEP
mOS was 11.8 mos in the D+EP arm vs 9.1 mos in the EP arm (HR 0.61;
95% CI 0.40-0.92). Prevalence of neuroendocrine (ASCL1, NEUROD1)
and non-neuroendocrine subtypes (POU2F3, YAP1 [Rudin] or Inamed
[Gay]) was similar in both methods. ASCL1 was more prevalent and
NEUROD1 less prevalent with the Rudin method. Inamed and YAP1
subtypes (11% and 8% prevalence) showed high concordance between
methods. Using either method mOS in the D+EP arm was higher in the
Inamed or YAP1 subtype vs the other 3 subtypes.
Conclusions: Among the 4 subtypes the Inamed/YAP1 subtype showed
the longest OS in the D+EP arm; this may represent a subgroup primed to
respond to immunotherapy. Despite the limited sample size this nding is
consistent with other studies.
Reference: Xie M. et al, AACR 2022
Funding: AstraZeneca
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
1066
Prospective real-world cohort of immuno-(chemo) therapy
(IO) prior to resection, denitive chemo-radiotherapy (CRT), or
palliative therapy in patients with non-small cell lung cancer
(NSCLC) without a primary curative option
Karoline Lehrach1; Sabine Fallscheer2; Birgit Schwenk2; Sebastian
Kramberg2; Jörn Sträter3; Susanne Eschmann4; Rainer Sätzler1;
Frank Heinzelmann5; Martin Faehling2
1Klinik für Thoraxchirurgie, Klinikum Esslingen, Esslingen am Neckar,
Deutschland
2Klinik für Kardiologie und Pneumologie, Klinikum Esslingen, Esslingen am
Neckar, Deutschland
3Institut für Pathologie, Esslingen am Neckar, Deutschland
4MVZ Nuklearmedizin, Marienhospital, Stuttgart,
5MVZ Strahlentherapie, Klinikum Esslingen, Esslingen am Neckar, Deutschland
Background: Recent trials of IO prior to resection in locally advanced
resectable NSCLC report high rates of pathological response and prom-
ising survival. However, primarily irresectable patients were excluded.
Moreover, there is no data on CRT aer IO in patients who are primar-
ily not amenable to CRT. We hypothesized that induction IO may enable
NSCLC patients with a potentially curative stage including oligomet-
astatic disease (II – IVB [M1b]), for whom primary curative treatment
(resection or CRT) is not possible for anatomical or functional reasons, to
receive curative treatment.
Methods: We enrolled 59 NSCLC patients with aforementioned charac-
teristics into a prospective real-world cohort of induction IO followed by
morphologic and metabolic reassessment and multidisciplinary board-
guided curative treatment (resection [preferred] or CRT) or palliative
therapy. Primary endpoint was the proportion of patients receiving cura-
tive treatment. Results of the rst 35 patients have been published recently
(KOMPASS-neo trial, Faehling (2021), EJC 156:175).
Results: 56 patients (95%) received curative treatment (23 R0 resections,
33 CRT). Of the completely resected patients, 11 had a major pathological
response, including 9 with a pathological complete response. ere were
23 recurrences: 3 (13%) in resected patients, 17 (52%) in CRT-patients,
and 3 (100%) in palliative patients (FU 15 months). 21 deaths occurred
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 145
(15 tumor-related deaths: 12 in CRT patients, and 3 in palliative patients;
2 treatment-related deaths (1 peri-operative, 1 RT pneumonitis); 4 other
causes).
Conclusions: In locally advanced or oligometastatic NSCLC without a
primary curative option, induction IO results in a high rate of curative
treatment with promising early survival data. Resected patients achieved
a high rate of prognostically favorable pathological response.
Disclosure Statement: e authors declare the following: MF is PI in phase 2 – 3
clinical trials by AstraZeneca, BMS, MSD, and Roche, for which payments were
made to my institution. He has received payment for advisory boards and speaker’s
honoraria by AstraZeneca, BMS, MSD, and Roche. Attendance of the virtual
WCLC 2020 was supported by AstraZeneca. SK reports speaker’s honoraria by
Roche.
Poster
16
Durvalumab ± tremelimumab + chemotherapy as rst-line
treatment for mNSCLC: results from the Phase 3 POSEIDON
study
Jens Kern1; Melissa L. Johnson2; Byoung Chul Cho3; Alexander Luft4;
Jorge Alatorre-Alexander5; Sarayut Lucien Geater6; Konstantin Laktionov7;
Aleksandr Vasiliev8; Sang-We Kim9; Grygorii Ursol10; Maen Hussein11;
Farah Louise Lim12; Cheng-Ta Yang13; Luiz Henrique Araujo14;
Haruhiro Saito15; Niels Reinmuth16; Xiaojin Shi17; Lynne Poole18;
Nenad Medic18; Solange Peters19; Edward B Garon20; Tony Mok21;
Michael Thomas22
1Standort Missioklinik, Klinikum Würzburg Mitte gGmbH, Würzburg,
Deutschland
2Sarah Cannon Research Institute, Nashville, USA
3Yonsei Cancer Center, Seoul, Republik Korea
4Leningrad Regional Clinical Hospital, St. Petersburg, Russische Föderation
5Health Pharma Professional Research, Mexico City, Mexiko
6Prince of Songkla University, Songkhla, Thailand
7Federal State Budgetary InstitutionN.N. Blokhin National Medical Research
Center of Oncologyof the Ministry of Health of the Russian Federation (N.N.
Blokhin NMRCO), Moskau, Russische Föderation
8Private Health InstitutionClinical HospitalRZD-Medicine”, St. Petersburg,
Russische Föderation
9Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republik
Korea
10Acinus, Kropyvnytskyi, Ukraine
11Florida Cancer SpecialistsSarah Cannon Research Institute, Leesburg, USA
12Queen Mary University of London, London, Vereinigtes Königreich
13Chang Gung Memorial Hospital, Taoyuan City, Taiwan
14Instituto Nacional de Cancer-INCA, Rio de Janeiro, Brasilien
15Kanagawa Cancer Center, Yokohama, Japan
16Asklepios Lung Clinic, Munich-Gauting, Deutschland
17AstraZeneca, Gaithersburg, USA
18AstraZeneca, Cambridge, Vereinigtes Königreich
19Centre Hospitalier Universitaire Vaudois, Lausanne University, Lausanne,
Schweiz
20David Geen School of Medicine at UCLA, Los Angeles, USA
21Chinese University of Hong Kong, Hong Kong, China, VR
22Thoraxklinik Heidelberg gGmbH , Universitätsklinikum Heidelberg, Heidelberg,
Deutschland
Introduction: Immunotherapies targeting the PD-1/PD-L1 pathway
have transformed the treatment of metastatic NSCLC (mNSCLC) as
monotherapy and in combination with chemotherapy (CT). POSEIDON
(NCT03164616) is a randomized, open label, global phase 3 study evalu-
ating durvalumab (D) ± tremelimumab (T) in combination CT regimens
as 1L treatment for squamous or non-squamous mNSCLC.
Methods: Patients (pts) with treatment-naïve, EGFR/ALK wildtype mNS-
CLC were randomized (1:1:1) to receive: D 1500 mg + CT q3w for 4 cycles
followed by D 1500 mg q4w until progression; D 1500 mg + T 75 mg with
CT q3w for up to 4 cycles, followed by D 1500 mg q4w until progres-
sion, with one additional dose of T post CT; or CT q3w for up to 6 cycles.
Primary endpoints were PFS by BICR and OS for D+CT versus CT, posi-
tivity for either of which triggered analysis of the key secondary endpoints
PFS by BICR and OS for D+T+CT versus CT. Global health status/QoL,
functioning and symptoms were assessed using EORTC QLQ-C30/LC13.
Results: 1013 pts were randomized. 28.8% had PD-L1 TC 50%, 49.6% had
stage IVB disease, and 36.9% had squamous histology. PFS was signi-
cantly improved with D+CT versus CT, with a trend for OS improvement
that did not reach statistical signicance. Both OS and PFS were statisti-
cally signicantly improved with D+T+CT versus CT. e incidence of
Grade 3/4 treatment-related AEs (TRAEs) was 44.6%, 51.8%, and 44.4%
with D+CT, T+D+CT and CT, respectively, and 14.1%, 15.5% and 9.9% of
patients had TRAEs leading to any study treatment discontinuation. Pts in
the D+CT and T+D+CT arms tended to have longer time to deterioration
and greater rates of improvement in global health status/QoL, functioning
and symptoms vs pts in the CT arm.
Conclusion: D+T+CT demonstrated statistically signicant improve-
ments in both PFS and OS versus CT in pts with mNSCLC. Overall, the
safety prole was similar across all three arms, with no new safety signals
identied; treatment discontinuation rates were similar with D+CT and
T+D+CT.
Reference:
Johnson, M. et al, WCLC 2021, LBA #833 and Garon, EB. Et al, ELCC 2022 #243
Funding: AstraZeneca
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
33
Atezolizumab (atezo) vs best supportive care (BSC)
in stage II-IIIA NSCLC with high PD-L1 expression:
sub-analysis from the pivotal phase III IMpower010 study
Enriqueta Felip1; Nasser Altorki2; Caicun Zhou3; Eric Vallieres4;
Ihor Vynnychenko5; Andrey Akopov6; Alex Martinez-Marti1;
Antonio Chella7; Igor Bondarenko8; Grygorii Ursol9; Evgeny Levchenko10;
Nikolay Kislov11; Rüdiger Liersch12; Rossella Belleli13; Virginia Mcnally14;
Elizabeth Bennett15; Barbara Gitlitz15; Heather Wakelee16
1Vall dHebron Institute of Oncology , Vall dHebron University, Barcelona,
Spanien
2Weill Cornell Medicine, New York, USA
3Tongji University Aliated Shanghai Pulmonary Hospital, Shanghai, China, VR
4Swedish Cancer Institute, Seattle, USA
5Regional Municipal Institution Sumy Regional Clinical Oncology Dispensary,
Sumy State University, Sumy, Ukraine
6Pavlov State Medical University, Saint Petersburg, Russische Föderation
7Azienda Ospedaliero Universitaria Pisana, Pisa, Italien
8Dnipro State Medical University, Dnipro, Ukraine
9Acinus, Kropyvnytskyi, Ukraine
10N.N. Petrov National Medical Research Center of Oncology, St Petersburg,
Russische Föderation
11Regional Clinical Oncology Hospital, Yaroslavl, Russische Föderation
12Clemenshospital Münster, Münster, Deutschland
13F. Homann-La Roche Ltd, Basel, Schweiz
14Roche Products Ltd, Welwyn Garden City, Vereinigtes Königreich
15Genentech Inc., South San Francisco, USA
16Stanford Cancer Institute, Stanford, USA
Background: IMpower010 showed signicant DFS benet with atezo aer
adjuvant chemo in resected NSCLC (Felip Lancet 2021). At the interim
DFS analysis, the signicance boundary was crossed for the stage II-IIIA
PD-L1 TC≥1% population (stratied HR, 0.66; 95% CI: 0.50, 0.88), with
greatest benet in the PD-L1 TC≥50% subgroup (unstratied HR, 0.43;
95% CI: 0.27, 0.68). Here we present further analyses in PD-L1 TC ≥50%
stage II-IIIA NSCLC pts.
Methods: IMpower010 (NCT02486718) study design and primary DFS
analysis details have been reported (Felip Lancet 2021). DFS in PD-L1
TC ≥50% (VENTANA SP263) stage II-IIIA (UICC/AJCC v7) pts was a
prespecied secondary endpoint; additional subgroup data reported are
exploratory.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts146
Result: Baseline characteristics were generally balanced for atezo- vs BSC-
arm pts with PD-L1 TC ≥50% stage II-IIIA NSCLC. Median follow-up
was 34.2 mo (21 Jan 2021 cuto). Pts beneted throughout most sub-
groups including squamous (HR, 0.60; 95% CI: 0.29, 1.26) and nonsqua-
mous (HR, 0.36; 95% CI: 0.20, 0.65) histology; stage II (HR, 0.51; 95%
CI:0.26, 1.00) and stage IIIA (HR, 0.38; 95% CI: 0.20, 0.72); N1 (HR, 0.29;
95% CI: 0.12, 0.72) and N2 (HR, 0.35; 95% CI: 0.18, 0.68) status. Safety in
PD-L1 TC≥50% stage II-IIIA pts was consistent with that of the overall
population and known safety prole of atezo. Initial disease relapse was
locoregional-only in 15/25 atezo-arm pts (60%) vs 17/50 BSC-arm pts
(34%) and distant-only in 6/25 (24%) vs 21/50 (42%); CNS-only relapse
was seen in 1/25 (4%) vs 7/50 (14%).
Discussion: Data from other randomised phase 3 adjuvant studies of
PD-1/PD-L1 inhibitors will further elucidate the role of CIT in the adju-
vant setting in eNSCLC.
Conclusion: IMpower010 pts with PD-L1 TC≥50% stage II-IIIA NSCLC
derived DFS benet with atezo vs BSC at the interim DFS analysis. Data
were consistent across most subgroups, albeit with limited pt numbers in
this post hoc analysis. Numerically, more distant and CNS relapses were
seen with BSC. e tolerability prole of atezo was in line with the overall
population, demonstrating a positive benet-risk prole.
Disclosure Statement: e authors declare the following: Honorare von AbbVie,
Astra Zeneca, BMS, Boehringer Ingelheim, Daichi Sankyo, Eli Lilly, MSD, Novar-
tis, Pzer, Roche
47
Clinical observation after combined pulmonary Stereotactic
Radiotherapy (SBRT) and mediastinal conventionally
fractionated Volumetric Arc Therapy (VMAT) in advanced
Non-Small Cell Lung Cancer (NSCLC)
Cedric Stüwe1,2; Tanja Eichkorn1,2; Eric Tonndorf-Martini1,2; Kai Schubert1,2;
Sebastian Regnery1,2; Thomas Held1,2; Farastuk Bozorgmehr3,4;
Petros Christopoulos3,4; Laila König1,2; Patrick Naumann1,2;
Sebastian Adeberg1,2; Klaus Herfarth1,2; Michael Thomas3,4; Stefan Rieken5;
Jürgen Peter Debus1,2,4,6 7; Rami A. El Shae5
1Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg,
Deutschland
2National Center for Radiation Oncology (NCRO), Heidelberg Institute for
Radiation Oncology (HIRO), Heidelberg, Deutschland
3Thoracic Clinic, Heidelberg University, Heidelberg,
4National Center for Tumor diseases (NCT), Heidelberg University, Heidelberg,
Deutschland
5Department of Radiation Oncology, Göttingen University Hospital, Göttingen,
Deutschland
6Clinical Cooperation Unit Radiation Oncology (E050), German Cancer Research
Center (DKFZ), Heidelberg, Deutschland
7Deutsches Konsortium für Translationale Krebsforschung (DKTK), German
Cancer Research Center (DKFZ), Heidelberg, Deutschland
Background: Rates for pneumonitis in radiotherapy of the lung dif-
fer widely depending on the irradiated lung volume and dose exposure.
Other factors such as chemotherapy, or pulmonary diseases are shown to
further increase pneumonitis rates. In patients with peripherally located
advanced stage Non-small Cell Lung Cancer, large target volumes or
pre-existing pulmonary conditions can necessitate dose reductions to
reduce toxicity.
Methods: 21 patients with stage III or oligometastatic stage IV NSCLC
with peripherally located primary where a single target volume resulted
in clinically unacceptable dose exposure of the lungs were treated with
denitive radio(chemo)therapy using conventionally fractionated medi-
astinal volumetric arc radiotherapy (VMAT) in combination with stereo-
tactic radiotherapy (SBRT) for the primary. Patients were retrospectively
observed for a median of 2.7 years (range: 2.4 months - 5,8 years) using
medical and ocial records.
Results: Median patient age was 63.3 years (IQR 56-73). 85% of patients
received simultaneous or sequential platinum-based chemotherapy.
Median overall survival and median progression-free survival were 3.4
years (range: 2.4 months - 5.8 years) and 1.2 years (range: 1 month - 5.2
years), respectively. Median intrathoracic progression-free survival and
median primary tumor progression-free survival were not reached during
the follow-up period. In two cases (10%), pneumonitis occurred with one
being graded as CTCAE grade 1 and one being graded as CTCAE grade 3.
Grade 3 pneumonitis was treated with corticosteroids and antibiotics and
grade I pneumonitis remitted without further treatment.
Discussion: Pneumonitis probability seems to be reduced without impair-
ments in tumor control with this tissue-sparing radiotherapy approach.
Conclusion: Conventionally fractionated mediastinal VMAT in combina-
tion with SBRT for the primary is feasible and could reduce pneumonitis
rates in a patient cohort unsuitable for the conventional radiotherapy due
to otherwise large target volumes or pre-existing pulmonary conditions.
Disclosure Statement: e authors declare no conict of interest.
50
Neoadjuvant Osimertinib with/without Chemotherapy
vs Chemotherapy for EGFR Mutated Resectable NSCLC:
NeoADAURA
Frank Griesinger1; Masahiro Tsuboi2; Walter Weder3; Carles Escriu4,
Collin Blakely5; Jianxing He6; Sanja Dacic7; Yasushi Yatabe8,
Lingmin Zeng9; Andrew Walding10; Jamie Chaft11
1Pius-Hospital Oldenburg, Oldenburg, Deutschland
2National Cancer Center Hospital East, Kashiwa, Japan
3Department of Thoracic Surgery, Thoraxchirurgie, Klinik Bethanien, Zürich,
Schweiz
4The Clatterbridge Cancer Centre, Bebington, Wirral, Vereinigtes Königreich
5Department of Medicine, University of California, San Francisco, CA, USA
6The First Aliated Hospital Of Guangzhou Medical University, Guangzhou,
China, VR
7Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh,
PA, USA
8Department of Diagnostic Pathology, National Cancer Center, Tokyo, Japan
9Late Oncology Statistics, AstraZeneca, Gaithersburg, MD, USA
10AstraZeneca R&D, Alderley Park, Vereinigtes Königreich
11Memorial Sloan Kettering Cancer Center, New York, NY, USA
Background: Ca. 30% of NSCLC patients present in resectable stages.
Prim. treatment is curative surgery; prognosis aer surgery alone remains
poor. Neoadj. chemo. is recommended in resectable St. III NSCLC, regard-
less of EGFR status, and has shown clinical benet. Recent studies indicate
that EGFR-TKI could potentially reduce tumor size and clear microme-
tastases before surgery. Osimertinib is a 3rd-Gen., CNS-active EGFR-TKI,
with superior ecacy to other EGFR-TKIs in treatment-naïve EGFRm
adv. NSCLC. In the Ph. III ADAURA trial (NCT02511106), osimertinib
showed sig. DFS improvement (HR: 0.20 [99.12% CI 0.14, 0.30; p<0.001)
in resected IB-IIIA EGFRm NSCLC following adj. chemo, if indicated.
NeoADAURA (NCT04351555) is a Ph. III, controlled, randomized study
assessing ecacy and safety of osimertinib (+/- chemo) vs chemo + pla-
cebo as neoadj. treatment in resectable St. II-IIIB EGFRm NSCLC.
Methods: Eligible pts: ≥18 yrs (≥20 yrs, Japan), ECOG PS 0/1, prim.
non-sq. St. II-IIIB (IASLC Cancer Staging Manual v8) NSCLC and con-
rmed EGFRm, deemed completely resectable. No prior treatment with
systemic therapy for NSCLC is allowed. Ca. 351 pts will be randomized
1:1:1 to receive platinum-based chemo (pemetrexed 500 mg/m2 + car-
boplatin AUC5 or cisplatin 75 mg/m2) + placebo (Arm 1; double-blind),
platinum-based chemo + osimertinib 80 mg QD (Arm 2; double-blind)
or osimertinib 80 mg QD alone (Arm 3; open-label). Pts will be stratied
by disease St. (II/III), race (non-Asian/Chinese/other Asian) and EGFR
mutation (Ex19del/L858R). Following 3 cycles of chemo (Arms 1 and 2)
or 9 weeks of osimertinib (Arm 3), pts will undergo surgical resection of
prim. NSCLC. Treatment with osimertinib or placebo may continue until
surgery. Post-surgery, pts will receive optimal care (investigator-dened);
this may include adj. osimertinib treatment for 3 yrs (max.)/until recur-
rence or unmanageable toxicity. Prim. endpoint is MPR (≤10% residual
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 147
cancer cells in surgical specimen). Secondary endpoints: pCR, EFS, down-
staging, DFS, OS, safety.
Originally presented at WCLC 2020
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
78
Patterns of pretreatment diagnostic assessment in patients
treated with stereotactic body radiotherapy (SBRT) for
non-small cell lung cancer (NSCLC): special characteristics
in the COVID-19 pandemic and inuence of parameters on
outcomes
Felix-Nikolai Oschinka Jegor Habermann1,2; Daniela Schmitt1,2;
Thomas Failing1,2; Jann Fischer1,2; Sandra Donath1,2;
Markus Anton Schirmer1,2; Manuel Guhlich1,2; Niklas Josua Alt1,2;
Julian Muster1,2; Rami El Shae1,2; Stefan Rieken1,2; Martin Leu1,2;
Leif Hendrik Dröge1,2
1Universitätsmedizin Göttingen, Klinik für Strahlentherapie und Radioonkologie,
Göttingen, Deutschland
2University Medical Center Göttingen, Comprehensive Cancer Center
Niedersachsen, Göttingen, Deutschland
Background: e pandemic raised a discussion about postponement of
medical interventions for lung cancer. We analyzed the special charac-
teristics of pretreatment diagnostic assessment in the pandemic and the
inuence of diagnostic assessment on outcomes.
Methods: A total of 96 patients with stereotactic body radiotherapy
(SBRT) for non-small cell lung cancer (NSCLC) were included. We com-
pared characteristics in the pre-COVID era (2012-2019) and characteris-
tics in the COVID era (2020-2021). We analyzed whether pretreatment
diagnostic assessment and the time from assessment to SBRT initiation
had an inuence on outcomes.
Results: e number of patients per month with SBRT was higher in the
COVID era (mean 1.5) than in the pre-COVID era (mean 0.9) (p=0.04).
In the COVID era, we found longer times from the planning CT scan to
the initiation of SBRT (p<0.001, mean, 3.0 vs. 1.7 weeks). Patients who
received a pretreatment PET/CT scan (n=83) experienced better overall
survival (p=0.02, 2 years, 61% vs. 29%) than patients who underwent
conventional staging (n=13). A longer time from the PET/CT scan to the
initiation of SBRT (<10 vs. ≥10 weeks) was associated with worse locore-
gional control (p=0.01, 2 years, 97% vs. 70%).
Discussion: e pandemic raised the question whether medical interven-
tions can safely be postponed. At the same time, patients are at risk of
tumor progression. Lung SBRT can be performed as an outpatient pro-
cedure with less close contacts. e preference to refer patients to SBRT
might explain the increase in patients treated in the COVID era. e lon-
ger times from the planning CT scan to SBRT might reect the eorts to
slow the virus spread. Our study points out that eorts should be made to
obtain a PET/CT scan close to SBRT.
Conclusion: e ndings on special characteristics of management
during the COVID era might serve as a basis to guide strategies in similar
future scenarios. e postponement of interventions should be carefully
discussed with consideration of an accurate and timely staging workup.
Disclosure Statement: e authors declare no conict of interest.
94
Predictive value of mRNA expression and dynamic changes
from immune related biomarkers in liquid biopsies before and
after start of pembrolizumab in stage IV non-small cell lung
cancer (NSCLC)
Natalie Brückl1; Ralph Wirtz2; Elke Veltrup2; Christian Meyer3;
Gloria Zeitler4; Dieter Wuerein4; Fabian Reich4; Joachim Ficker4;
Sebastian Eidt1; Wolfgang Brückl4
1Institut für Pathologie, St. Elisabeth Krankenhaus Köln, Lehrkrankenhaus
Universität Köln
2Institut für Pathologie, St. Elisabeth Krankenhaus Köln, STRATIFYER Molecular
Pathology GmbH, Köln
3Institut für Pathologie, Klinikum Nürnberg, Paracelus Medizinische
Privatuniversität (PMU) Standort Nürnberg, Nürnberg
4Medizinische Klinik 3, Klinikum Nürnberg, Paracelus Medizinische
Privatuniversität (PMU) Standort Nürnberg, Nürnberg
Background: e aim of this study was to determine whether mRNA
expressions and dynamic changes of immune-related genes before and
aer starting rst-line treatment with the PD-1 inhibitor pembrolizumab
in patients with NSCLC were of predictive value.
Methods: CD3, CD8, PD-1, PD-L1 and CTLA-4 mRNA expression lev-
els were measured from peripheral blood before and aer three weeks
of treatment with the PD-1 inhibitor. Univariate and multivariate anal-
yses were performed retrospectively. Response, progression-free survival
(PFS) and overall survival (OS) were determined.
Results: In univariate analysis an increase of CD3 and CD8 mRNA
expression aer the rst cycle of pembrolizumab were each associated
with improved PFS and OS. In contrast, patients with no change or with a
decrease in CD3 and CD8 mRNA expression showed signicantly worse
outcome. CD8 mRNA increase remained an independent prognostic fac-
tor for PFS and OS in the multivariate analysis with p values of 0.011 and
0.006, respectively.
Conclusion: An increase of CD8 mRNA expression predicts favorable
outcome aer rst line monotherapy with pembrolizumab, while no
change or decrease might serve as an indicator of poor outcome and
might give cause for early treatment escalation for instance by addition of
chemotherapy or additional ICI treatment e.g. against CTLA-4.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
116
Durvalumab ± tremelimumab + platinum-etoposide in rst-
line extensive-stage SCLC (ES-SCLC): 36-monthoverall survival
from the Phase 3 CASPIAN study
Luis Paz-Ares1; Christian Schulz2
1Department of Medical Oncology, Madrid, Spanien
2University Hospital Regensburg, Regensburg, Deutschland
Background: Etoposide plus either cisplatin or carboplatin (EP) had been
the standard rst-line (1L) treatment for ES-SCLC, with limited alter-
native therapies for more than three decades, until recent progress with
immunotherapy in this setting. e Phase 3, randomised, open-label,
global CASPIAN study assessed EP ± durvalumab (D) ± tremelimumab
(T) as 1L treatment for patients with ES-SCLC, and D + EP demonstrated
a statistically signicant improvement in overall survival (OS) compared
with EP alone (data cut-o [DCO]: March 11, 2019): HR 0.73 (95% CI
0.59–0.91; p=0.0047). Aer a median follow-up of 25.1 months (DCO
Jan 27, 2020), the OS benet with D + EP vs EP was sustained (HR 0.75
[95% CI 0.62–0.91; nominal p=0.0032]), and D + T + EP numerically
improved OS vs EP (HR 0.82 [95% CI 0.68–1.00; p=0.0451]), but did not
reach statistical signicance (p≤0.0418) per prespecied statistical plan.
At 24 months, 22.2% of patients were alive in the D+ EP arm, 23.4% in
the D + T + EP arm, and 14.4% in the EP arm. Here we report updated
OS data from the CASPIAN study, aer a median follow-up of approx.
36months.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts148
Methods: In the CASPIAN study, 805 patients with treatment-naïve
ES-SCLC (WHO performance status 0/1) were randomised 1:1:1 to D
1500 mg + EP q3w, D 1500 mg + T 75 mg + EP q3w, or EP q3w, stratied
by planned platinum (investigator’s choice of carboplatin or cisplatin).
Patients in the immunotherapy arms received 4 cycles of EP + D ± T, fol-
lowed by maintenance D 1500 mg q4w until disease progression. Patients
in the D + T+ EP arm received an additional dose of T 75 mg aer EP.
Patients in the EP arm received up to 6 cycles of EP in total, and optional
prophylactic cranial irradiation at the investigator’s discretion. e two
primary endpoints were OS for D + EP vs EP and for D + T + EP vs EP.
Result: We present mature OS data for patients in the CASPIAN study,
based on a median follow-up duration of approx. 36 months.
Conclusion: is updated analysis of OS from the CASPIAN trial will
provide further insight into long-term survival benet with D + EP and D
+ T + EP vs EP in 1L treatment of patients with ES-SCLC.
Funded by AstraZeneca.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
135
Clinical Research platform Into molecular testing, treatment
and outcome of non-Small cell lung carcinoma Patients
(CRISP): First Real-World Evidence of NSCLC Stage II and III in
Germany - AIO-TRK-0315
Andreas Gröschel1; Bernward Passlick2; Martin Stuschke3;
Petros Christopoulos4; Martin Reck5; Christian Grah6; Annika Groth7;
Annette Hipper7; Marco Chiabudini8; Annette Fleitz8; Martina Jänicke8;
Lisa Spring8; Daniel Christoph9; Christiane Bernhardt10; Marcel Reiser11;
M.-O. Zahn12; Martin Sebastian13; Frank Griesinger14; Michael Thomas4;
Wilfried Eberhardt15
1Clemenshospital Münster, Klinik für Innere Med. II - Pneumologie und
Beatmungsmedizin, Münster, Deutschland
2Uniklinik Freiburg - Klinik für Thoraxchirurgie, Freiburg im Breisgau,
Deutschland
3Universitätsklinikum Essen, Westdeutsches Tumor Zentrum, Strahlenklinik,
Essen, Deutschland
4Thoraxklinik-Heidelberg, National Center for Tumor Diseases at Heidelberg
University Hospital, Translational Lung Research Center Heidelberg (TLRC-H),
member of the German Center for Lung Research (DZL), Heidelberg,
Deutschland
5LungenClinic Grosshansdorf, Großhansdorf, Deutschland
6Gemeinschaftskrankenhaus Havelhöhe , Klinik für Anthroposophische Medizin,
Berlin, Deutschland
7AIO-Studien-gGmbH, Berlin, Deutschland
8iOMEDICO, Freiburg im Breisgau, Deutschland
9MVZ für Hämatologie und Onkologie Essen gGmbH, Essen, Deutschland
10Gemeinschaftspraxis für Hämatologie und Onkologie, Dortmund, Deutschland
11PIOH - Praxis Internistische, Onkologie und Hämatologie, Köln, Deutschland
12Überörtliche Berufsausübungsgemeinschaft, MVZ Onkologische Kooperation,
Goslar, Deutschland
13Universitätsklinikum Frankfurt, Medizinische Klinik 2 Hämatologie/Onkologie,
Frankfurt am Main, Deutschland
14Pius-Hospital Oldenburg, Klinik für Hämatologie und Onkologie, Oldenburg,
Deutschland
15Ruhrlandklinik, Westdeutsches Lungenzentrum, Essen, Deutschland
Background: CRISP is a non-interventional, prospective, multi-center
clinical research platform whose aim is to understand the treatment real-
ity of patients (pts) with lung cancer in Germany. Here we present data of
pts diagnosed with early-stage NSCLC.
Methods: Since August 2018 106 sites in Germany have recruited about
1400 pts diagnosed with NSCLC stage I-III. Basic demographic data,
details about treatment reality, outcome and PRO data are collected and
analyzed. Here we show data on the rst 810 pts followed until June 2021.
Results: 26% of pts were diagnosed with stage II (5% stage IIA, 21% stage
IIB), 66% with stage III (32% stage IIIA, 34% stage IIIB/C).
Characteristics at diagnosis were: median age 66 years, 38% female, 83%
ECOG 0/1, 80% with comorbidities, 47% Charslon Comorbidity Index
of 0; 25% current smokers; 44%, heavy ex-smokers, 9% never-smokers.
Most of pts with tumors in clinical stage II underwent surgery (84%,
n=157) followed by adjuvant chemotherapy (CTx) (75%, n=140). e
2-year relapse-free survival (RFS) rate was 77% and the 2-year overall sur-
vival (OS) rate was 90%.
For pts with clinical stage IIIA tumors the most frequent treatment strat-
egy was also surgery (53%, n=124) followed by adjuvant CTx (37%, n=88);
the 2-year RFS rate was 52%, and the 2-year OS rate was 79%. 27% (n=64)
of pts with stage IIIA received denitive radiochemotherapy (RTCTx).
For pts with stage IIIB/C tumors the most frequent treatment was deni-
tive RTCTx (n=131, 53%); 26% (n=64) started with CTx, and 18% (n=44)
had surgery (followed mostly by CTx, n=36, 15%).
80% (n=131) of pts with an inoperable stage III tumor who received
RTCTx were tested for PD-L1 expression. 80 pts had a positive PD-L1
expression. 44 pts out of 68 eligible (best response CR/PR/SD) received
consolidation therapy with durvalumab.
Conclusion: CRISP presents comprehensive current real-life data of
patients with NSCLC in stage II or III covering all treatment settings in
Germany. With a longer recruitment time data on patients with stage I
will be analyzed.
Indication of source: ESMO Congress 2021 (data updated)
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
209
Breaking the crosstalk of the Cellular Tumorigenic Network in
NSCLC by a highly eective drug combination
Dennis Gürgen1; Theresia Conrad1; Michael Becker1; Susanne Sebens2;
Christoph Röcken3; Jens Homann1; Stefan Langhammer4
1EPO Experimental Pharmacology & Oncology GmbH, Berlin, Deutschland
2Institute for Experimental Cancer Research, Kiel University and University
Hospital Schleswig-Holstein, Campus Kiel, Kiel, Deutschland
3Institute for Pathology, Kiel University, Kiel, Deutschland
4life science consulting, Burgwedel, Deutschland
Background: Non-small cell lung cancer (NSCLC) is commonly diag-
nosed at advanced stages with limited treatment options particularly in
tumors without targetable driver mutations.
Methods: Considering previously published criteria for selecting drug
combinations for overcoming drug resistances, we have established a low
dose combination therapy with cabozantinib, afatinib, etoricoxib and
plerixafor. Utilizing NSCLC patient-derived xenogra (PDX) models we
aimed to use this drug regimen to disrupt paracrine substitutional sig-
naling within the Cellular Tumorigenic Network in order to circumvent
pre-existing and adaptive drug resistances.
Result: All PDX tumors treated, including highly therapy-resistant adeno-
and squamous cell carcinomas without identiable driver mutations,
were completely suppressed by this drug regimen leading to an Objective
Response Rate of 81% and a Clinical Benet Rate of 100%. Aer treat-
ment discontinuation growth suppression remained until the end of the
follow-up period with only slight increase in tumor growth. e applica-
tion and the safety prole of this low dose therapy regimen was well man-
ageable and without pronounced side eects in this pre-clinical setting.
Discussion: For the rst time we show that simultaneous inhibition of
pathways forming the Cellular Tumorigenic Network in NSCLC tumors
is highly eective and overcomes drug resistances for monotherapies. All
of the drugs used in this combination regimen are approved for dierent
indications and therefore readily available.
Conclusion: Our results emphatically encourage a setup for a clinical
study in advanced stage NSCLC patients without targetable driver muta-
tions combining the drugs cabozantinib, afatinib, plerixafor and etoricoxib
in a low dose treatment regimen as novel therapy strategy.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 149
Indication of Source: Gürgen et al. Breaking the crosstalk of the Cellular
Tumorigenic Network by low-dose combination therapy in lung cancer
patient-derived xenogras.Commun Biol. 5:59, 2022.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
218
Early circulatingtumourDNA (ctDNA) dynamics for
predicting and monitoring response to immunotherapy(IO) vs
chemotherapy (CT) in patients with 1L metastatic (m) NSCLC:
analyses from the Phase 3 MYSTIC trial
S. Peters1; N. Rizvi2; M. Kuziora3; Z. Lai4; Y. Shrestha3; A. Dey5; J.C. Barrett3;
U. Scheuring6; L. Poole7; C. Abbosh8; R. Raja3; M. Hellmann9; J. Panse10
1Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne University,
Department of Oncology, Lausanne, Schweiz
2Columbia University Medical Center, Division of Hematology/Oncology,
NewYork, USA
3AstraZeneca, Translational Medicine, Gaithersburg, USA
4AstraZeneca, Translational Medicine, Waltham, USA
5AstraZeneca, Clinical Pharmacology and Quantitative Pharmacology,
Waltham,USA
6AstraZeneca, Global Medicines Development, Cambridge, Vereinigtes
Königreich
7AstraZeneca, Biostatistics, Cambridge, Vereinigtes Königreich
8University College London Cancer Institute, Cancer Research UK Lung Cancer
Centre of Excellence, London, Vereinigtes Königreich
9Memorial Sloan Kettering Cancer Center, Thoracic Oncology Service, Division of
Solid Tumor Oncology, Department of Medicine, New York, USA
10Uniklinik RWTH Aachen, Oncology, Hemostaseology and Stem Cell
Transplantation, Aachen, Deutschland
Background: We have previously shown that ctDNA dynamics can
identify pts as “molecular responders” (MRs) to IO who have improved
OS compared with molecular non-responders (non-MRs). Larger ran-
domized studies in specic clinical settings including 1L are needed to
optimize use of ctDNA as a biomarker of response. We report analyses
of ctDNA in pts with mNSCLC treated with 1L durvalumab (D), D +
tremelimumab (T), or CT in the phase 3 MYSTIC trial.
Methods: Plasma was collected at baseline (BL) and on-treatment (pre-
dose at cycle 2 of D ± T/cycle 3 of CT) and ctDNA was sequenced using
the Guardant OMNI panel (500 genes). Mean variant allelic frequency
(VAF) values of BL variants with ≥ 0.3% VAF and the change between BL
and on-treatment were used to calculate delta VAF. MRs were dened as
having a decrease of ≥ 50% from BL mean VAF.
Results: Biomarker evaluable populations (BEPs) with variants ≥0.3%
VAF were n=901 for BL (BEP1) and n=713 for BL + on-treatment (BEP2).
Both BEPs were similar to the ITT population. Pts with BL mean VAF <
median had longer OS/PFS vs ≥ median in all arms. MRs had longer OS vs
non-MRs with D (HR 0.41, 95% CI 0.28–0.6) and D + T (0.37, 0.26–0.53)
but not CT (1.1, 0.84–1.5); PFS results were similar. At wk 6, MRs had
higher partial response (PR) rates vs non-MRs with D (odds ratio [OR]
4.4, 95% CI 1.7–11.6), D + T (8.7, 3.4–25.5), and CT (8.0, 2.7–32.2); the %
of PD was lower among MRs vs non-MRs with D ± T but not CT. Among
radiologic responders (PR/complete response by BICR), MRs were more
likely to achieve durable response (>6 months) vs non-MRs with D (OR
4.4, 95% CI 2.1–9.4) and D + T (6.8, 3.2–15.2) with a weaker trend for CT
(2.9, 0.91–12.5). Among pts with SD at wk 6, MRs had longer OS vs non-
MRs with D (HR 0.51, 95% CI 0.31–0.86) and D + T (0.58, 0.36–0.94) but
not CT (1.2, 0.83–1.7).
Conclusions: Results indicate that BL ctDNA level is prognostic in 1L
mNSCLC; further, MR is predictive of clinical benet with IO but not CT.
On-treatment ctDNA dynamics may have important predictive value for
long-term outcomes with IO, complementing radiologic assessment and
enabling early decision-making.
Funding: AstraZeneca
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
255
Durability of Ecacy with Selpercatinib in Patients (pts) with
RET Fusion+ Non-Small-Cell Lung Cancer (NSCLC)
Alexander E. Drillon1; Vivek Subbiah2; Oliver Gautschi3; Pascale Tomasini4;
Filippo G. De Braud5; Benjamin Solomon6; Daniel Shao-Weng Tan7;
Guzman Alonso8; Juergen Wolf9; Keunchil Park10; Koichi Goto11;
Victoria Soldatenkova12; Sylwia Szymczak12; Scott S. Barker12; Tarun Puri12;
Aimee K. Lin12; Herbert Loong13; Benjamin Besse14
1Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College,
NewYork, USA
2Department of Investigational Cancer Therapeutics, The University of Texas MD
Anderson Cancer Center, Houston, USA
3University of Berne and Cantonal Hospital of Lucerne, Lucerne, Schweiz
4Hôpitaux Universitaires, de Marseille Timone, Marseille, Frankreich
5Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei
Tumori, Milan, Italien
6Department of Medical Oncology and Research Division, Peter MacCallum
Cancer Centre and the Sir Peter MacCallum Department of Oncology, University
of Melbourne, Melbourne, Australien
7National Cancer Center, Singapore, Singapur
8Vall dHebron Institute of Oncology (VHIO), Vall dHebron Hospital Universitari,
Barcelona, Spanien
9Department of Internal Medicine, Center for Integrated Oncology, University
Hospital Cologne, Cologne, Deutschland
10Division of Hematology/Oncology, Samsung Medical Center, Sungkyunkwan
University School of Medicine, Seoul, Republik Korea
11National Cancer Center Hospital East, Kashiwa, Japan
12Eli Lilly and Company, Indianapolis, USA
13Chinese University of Hong Kong, Hongkong, China, VR
14Gustave Roussy UniversiteParis Sud, Paris, Frankreich
Background: Selpercatinib is approved in multiple countries for treat-
ment of RET fusion+ NSCLC.
Methods: Updated analysis of selpercatinib in pts with RET fusion+
NSCLC in LIBRETTO-001 was conducted with a 15-month (mo) inter-
val between preceding and current analyses. Primary endpoint: ORR by
IRC. Secondary endpoints included DoR, PFS, clinical benet rate (CBR;
CR+PR+SD≥16 weeks), OS and safety.
Result: Ecacy results for treatment naïve pts (N=69) are: ORR%
(95%CI)=84.1 (73.3–91.8) and CBR% (95%CI)=92.8 (83.9–97.6); ecacy
results for pts previously treated with platinum chemotherapy (N=247) are:
ORR% (95%CI)= 61.1(54.7–67.2) and CBR% (95%CI)=85.4(80.4–89.6).
Despite a median follow-up (f/u) of ~24 mo in the treatment naïve and
platinum chemotherapy pretreated populations, median DoR (mDoR)
and PFS(mPFS) estimates are still not mature. Among all NSCLC pts,
26 had measurable CNS metastases at baseline per IRC. Selpercatinib
treatment resulted in a CNS ORR=84.6%(95%CI=65.1–95.6), (CNS
mDoR=9.4 mo [95%CI=7.4–15.3] at a median follow-up [f/u]=25.8 mo).
safety population (NSCLC pts with ≥1 dose, N=356), most common AEs
in ≥25% pts: dry mouth, diarrhea, hypertension, increased ALT/AST,
peripheral edema, constipation, rash, headache, fatigue. 34 pts discon-
tinued treatment due to AEs, including 11 due to drug-related AEs per
investigator.
Conclusion: With longer f/u and additional patients, selpercatinib
demonstrates durable ecacy and intracranial activity regardless of line
of therapy. e safety prole of selpercatinib remains consistent with prior
reports.
Indication of source:
1 Previously presented at the IASLC-ESMO European Lung Cancer Conference
- 12th ELCC: March 2022, “FPN (Final Publication Number): 27P”, “Alexander
Drilon et al.” - Reused with permission
Disclosure Statement: e authors declare the following: Advisory boards and
lecture fees: Amgen, AstraZeneca, Bayer, Blueprint, BMS, Boehringer-Ingelheim,
Chugai, Daiichi Sankyo, Ignyta, Janssen, Lilly, Loxo, MSD, Novartis, Pzer, Roche,
Seattle Genetics, Takeda Research support (to institution); BMS, Janssen Pharma-
ceutica, Novartis, Pzer
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts150
256
Pacic-R Real-World Study: Treatment Duration and Interim
Analysis of Progression-Free Survival in Unresectable
Stage III NSCLC Patients Treated with Durvalumab After
Chemoradiotherapy
Daniel Christoph1; N. Girard2; H.J.M. Smit3; A. Sibille4; F. Mcdonald5;
F. Mornex6; M.C. Garassino7; A.R. Filippi8; S. Peters9; J.K. Field10;
V. Drageset Haakensen11; J. Bar12; C. Chouaid13; V. Bray14; S. Kao15;
W. Sawyer16; A. Allen17; M. Licour17; P. Garrido18; R. Fietkau19
1Department of Medical Oncology/Hematology, Evang. Kliniken Essen-Mitte,
Evang. Huyssens-Stiftung Essen Huttrop, Essen, Deutschland
2Institut du Thorax, Institut Curie & Montsouris, Paris, Frankreich
3Department of Pulmonary Diseases, Rijnstate Hospital, Arnheim, Niederlande
4Department of Pneumology and Allergology, Centre Hospitalier Universitaire
de Liège, Liegé, Belgien
5Lung Unit, The Royal Marsden NHS Foundation Trust, London, Vereinigtes
Königreich
6Department of Radiation Oncology, Centre Hospitalier Universitaire de Lyon,
Lyon, Frankreich
7Department of Hematology/Oncology, The University of Chicago, Chicago, USA
8Radiation Oncology Department, Fondazione IRCCS Policlinico San Matteo and
University of Pavia, Pavia, Italien
9Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV),
Lausanne, Schweiz
10Roy Castle Lung Cancer Research Programme, Department of Molecular
and Clinical Cancer Medicine, University of Liverpool, Liverpool, Vereinigtes
Königreich
11Department of Oncology, Oslo University Hospital, Oslo, Norwegen
12Institute of Oncology, Sheba Medical Centre, Ramat Gan, Israel
13Service de Pneumologie, CHI Créteil, Créteil, Frankreich
14Department of Medical Oncology, Liverpool Hospital, Liverpool, New South
Wales, Australien
15Department of Medical Oncology, Chris OBrien Lifehouse, Camperdown,
NewSouth Wales, Australien
16Medical Aairs, Oncology, AstraZeneca, Gaithersburg, MD, USA
17Medical Aairs, Oncology, AstraZeneca, Paris, Frankreich
18Hospital Ramón y Cajal, Universidad de Alcalá, Madrid, Spanien
19Department of Radiation Oncology, Universitätsklinikums Erlangen, Erlangen,
Deutschland
Background: Durvalumab (durva) consolidation therapy for up to 12
months(m) (PACIFIC regimen) is now standard of care in patients (pts)
with unresectable Stage III non-small-cell lung cancer (NSCLC) with-
out disease progression aer platinum-based (ptb) chemoradiotherapy
(CRT). PACIFIC-R assesses the eectiveness of durva in this pt popula-
tion in a real-life setting.
Methods: PACIFIC-R (NCT03798535) is a large international, observa-
tional study in pts who received ≥1 dose of durva (10 mg/kg Q2W) as part
of an AstraZeneca initiated expanded access program. Pts had completed
ptb-chemotherapy concurrent or sequential to radiotherapy within the
previous 12 weeks without evidence of disease progression.
Results: Outcomes were assessed in the full analysis set (N=1155).
Median time to durva initiation aer the end of RT was 52 days. Overall
median durva treatment duration was 337 days (11 m); 232 (20.1%) pts
received treatment for >12 m (50 [4.3%] for >14 m). Pts received a median
of 22 infusions. Reasons for/median time to treatment discontinuation
included completion of treatment (47.6%/11.8 m; investigator decision
per country protocol), disease progression (25.8%/5.1 m) and adverse
event (AE; 17.5%/2.8 m).
Pneumonitis was the most common AE leading to discontinuation (tem-
porary: 5.1%; permanent: 8.7%). 214 (18.5%) pts had any-grade pneumo-
nitis and/or interstitial lung disease (median time from durva start: 74
days [2.4 m]). Of these, most events were moderate (8.8%) in severity; 2
(0.2%) and 1 (0.1%) pts had a life-threatening or fatal event, respectively.
Interim analysis (51.8% of events) showed a median realworld(rw) PFS
(rwPFS) of 22.5 m (95% CI, 19.7-25.5). rwPFS by baseline PD-L1 status
and prior CRT will be included in the nal presentation.
Conclusions: ese results demonstrate the eectiveness of consolida-
tion durva aer CRT in a rw-cohort of pts with unresectable Stage III
NSCLC; pneumonitis events were mostly moderate in severity. Additional
data from an externally sponsored study with similar enrolment criteria in
Spain will be included in the nal presentation.
Disclosure Statement: e authors declare no conict of interest.
265
FINN (CA209-7MA): A non-interventional study (NIS) of rst-
line nivolumab plus ipilimumab combined with two cycles of
chemotherapy in metastatic non-small cell lung cancer
Sylvia Gütz1; Christian Schumann2; Harald Müller-Huesmann3; Daniela
Waldenberger4; Eckart Laack5
1St. Elisabeth-Krankenhaus Leipzig, Leipzig, Deutschland
2Klinikverbund Allgäu gGmbH, Kempten und Immenstadt, Deutschland
3Brüderkrankenhaus St. Josef, Paderborn, Deutschland
4Bristol-Myers Squibb, München, Deutschland
5Hämato-Onkologie Hamburg, Prof. Laack und Partner, Hamburg, Deutschland
Background: e immune checkpoint inhibitors nivolumab and ipilim-
umab have distinct but complementary mechanisms of action. Several
phase III and IV studies assessed the activity and safety of dual check-
point inhibitor blockade in the rst-line (1L) treatment of metastatic non-
small cell lung cancer (NSCLC). e randomized, open-label, phase III
CheckMate 9LA trial demonstrated a statistically signicant improvement
in overall survival, progression-free survival and overall response rate for
patients treated with nivolumab + ipilimumab combined with two cycles
of chemotherapy compared to chemotherapy alone. As the experience
with this combination therapy is mainly based on data from randomized
clinical trials, the NIS FINN was designed to collect real-life data during
the early post-market authorization approval period. e study aims to
describe patient characteristics and outcomes, safety prole, and treat-
ment patterns in normal clinical practice.
Methods: FINN (NCT04794010) is a national, prospective, observa-
tional, multicenter study. Overall, 825 patients diagnosed with metastatic
NSCLC, who start a systemic therapy with nivolumab + ipilimumab + 2
cycles of chemotherapy within the market authorization, will be enrolled.
e study collects data from approx. 80 oncology care facilities. Patients
will be followed for 5 years from Day 0 (ie, treatment initiation) until
death, withdrawal of consent, loss of follow-up, or end of the study.
During the follow-up period, assessments will be performed according
to routine local clinical practice. Data entry in the electronic case report
form (eCRF) will take place at Day 0, Week 6, Month 3, 6, 9, 12, 18, 24,
36, 48, and 60 (5 years aer nivolumab initiation). e primary objective
is overall survival. Secondary objectives include progression free survival,
treatment duration, patient characteristics, safety proles and patient-re-
ported outcomes (assessed by EQ-5D and NSCLC-Symptom Assessment
Questionnaire).
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 151
280
Checkpoint inhibitor monotherapy in potentially study-
eligible or non-study-eligible NSCLC patients in the German
CRISP Registry real-world cohort (AIO-TRK-0315)
Frank Griesinger1; Martin Sebastian2; Wolfgang Brückl3;
Horst-Dieter Hummel4; Bastian Jaeschke5; Jens Kern6; Class Wesseler7;
Martina Jänicke8; Annette Fleitz8; Stefan Zacharias8; Annette Hipper9;
Annika Groth9; Wilko Weichert10; Steen Dörfel11; Volker Petersen12;
Jan Schröder13; Jochen Wilke14; Wilfried Ernst Erich Eberhardt15;
Michael Thomas16
1Pius-Hospital Oldenburg, Hämatologie, Onkologie, Oldenburg, Deutschland
2Universitätsklinikum Frankfurt, Medizinische Klinik 2, Hämatologie, Onkologie,
Frankfurt am Main, Deutschland
3Klinikum Nürnberg Nord, Nordklinikum, Innere Medizin III - Schwerpunkt,
Pneumologie, Nürnberg, Deutschland
4Universitätsklinikum Würzburg, Interdisziplinäres Studienzentrum, mit ECTU,
Würzburg, Deutschland
5Helios Dr. Horst Schmidt Kliniken Wiesbaden, IM III: Hämatologie, Onkologie,
Palliativmedizin, Wiesbaden, Deutschland
6Klinikum Würzburg Mitte , Standort Missioklinik Med. Klinik, mit Schwerpunkt
Pneumologie, Würzburg, Deutschland
7Asklepios Klinikum Harburg, Klinik für Pneumologie, Hamburg, Deutschland
8iOMEDICO AG, Freiburg im Breisgau, Deutschland
9AIO-Studien-gGmbH, Berlin, Deutschland
10Klinikum rechts der Isar der Technischen Universität München, Pathologie,
München, Deutschland
11Onkozentrum Dresden, Dresden, Deutschland
12Onkologische Schwerpunktpraxis, Dr. med. Volker Petersen, Heidenheim
a.d.B., Deutschland
13Gemeinschaftspraxis für Hämatologie und internistische Onkologie, Mülheim
a.d.R., Deutschland
14Schwerpunktpraxis Hämatologie & Internistische Onkologie, Fürth,
Deutschland
15Universitätsklinikum Essen, Westdeutsches Tumor Zentrum, Essen,
Deutschland
16Thoraxklinik-Heidelberg, Thoraxonkologie, Heidelberg, Deutschland
Background: Treatment for metastatic non-small cell lung cancer
(NSCLC) stratied according to biomarker testing results was shown in
RCTs to have benecial outcomes. Whether these improvements carry
over into real-world routine therapy is of great interest for patients (pts)
and physicians. Here we used the CRISP registry to compare pts charac-
teristics (chr) and outcomes of pts with PD-L1 TPS≥50% tumors treated
with checkpoint inhibitor monotherapy (CPI) who are deemed either
potentially study-eligible (se) or non-se (n-se).
Methods: CRISP (NCT02622581) is a prospective, observational, multi-
center, interdisciplinary clinical research platform that collects data on all
(sequential) treatments, patient and tumor chr, biomarker testing, clin-
ical and patient-reported outcomes in ~180 hospitals and practices in
Germany. Of currently 6300+ pts recruited, data from 473 pts with PD-L1
TPS≥50% recruited 12/2015 to 06/2019, receiving CPI as 1st-line treat-
ment was analyzed. Pts with following chr were deemed se: ECOG=0-1,
stage IV, no brain metastases, no HIV, no 2nd-tumor, or prior (neo)adju-
vant therapy.
Result: Of 473 pts analyzed, 191 were se in reection of inclusion criteria
for RCTs KEYNOTE 42 and 24, 282 pts were n-se representing the real-
world population. Although both groups are similar in age, CR/PR rates
(1%[se] vs. 2%[n-se] and 21% vs. 22%) and rates of stopped treatments
because of toxicity (10%, both), se pts had a longer PFS (10.0 months
(mts), 95% CI: 7.6-15.2 vs. 7.9 mts, 95% CI: 6.0-10.6) and OS (23.3 mts,
95% CI: 16.5-26.1 vs. 20.2 mts, 95% CI: 15.9-26.2) than n-se pts.
Conclusion: In recent years the use of CPI monotherapy in PD-L1
TPS≥50% pts increased in Germany, resulting in improved treatment
outcome. Potentially study-eligible pts prot more than potentially
non-study-eligible pts. e impact of CPI combination therapies or treat-
ment without CPI on both pts groups, will be subject of future analyses.
Indication of source: ESMO congress 2021
Disclosure Statement: e authors declare no conict of interest.
337
Niraparib (Nira) + Pembrolizumab (Pembro) Versus Placebo
(PBO) + Pembro rst line (1L) Maintenance Therapy in
Advanced Non-Small Cell Lung Cancer (NSCLC): ZEAL-1L Phase
3 Study
Martin Schuler1; Suresh S. Ramalingam2; Lei Shi3;
Melissa Whipple Neibauer3; Tara Frenkl3; Alexander Stojadinovic3;
Solange Peters4
1West German Cancer Center, University Hospital Essen, Essen, Deutschland
2Emory University, Winship Cancer Institute, Atlanta, USA
3GlaxoSmithKline, Oncology, Philadelphia, USA
4Lausanne University, Oncology Department, Lausanne, Schweiz
Background: Poly (ADP-ribose) polymerase (PARP) inhibitor, Nira,
exerts antitumor activity by blocking homologous recombination DNA
damage repair. Nira crosses the blood-brain barrier in animal models,
extending activity to the central nervous system (CNS). In preclinical
cancer models, Nira activates the STING pathway, recruits T cells, and
upregulates programmed death ligand-1 (PD-L1). Synergistic antitu-
mor eects of Nira+Pembro (PD-1 inhibitor) have been observed in
triple-negative breast cancer and Platinum (Pt)-resistant ovarian cancer
(TOPACIO/KEYNOTE-162), and as 1L therapy in advanced/metastatic
NSCLC (JASPER), with a tolerable safety prole.
Methods: ZEAL-1L is a Phase 3 randomized, double-blind, global
trial comparing ecacy and safety of 1L maintenance therapy with
Nira+Pembro vs PBO+Pembro in patients with conrmed Stage IIIB–IV
NSCLC. Patients with no known driver mutation, and no disease progres-
sion aer 4–6 cycles of 1L induction Pt-based chemotherapy+Pembro will
be screened. Approximately 650 patients will be recruited for randomiza-
tion (1:1) to Nira (200/300 mg orally, daily)+Pembro or PBO+Pembro. All
patients will continue Pembro (200 mg IV) up to 35 cycles from the start
of 1L induction therapy. Treatment will continue until disease progres-
sion, unacceptable toxicity, death, or loss to follow-up.
Result: e primary endpoints are progression-free survival assessed by
Blinded Independent Central Review (BICR) per Response Evaluation
Criteria in Solid Tumors v1.1 criteria and overall survival. Key secondary
endpoint is time to CNS progression by BICR. Patient-reported outcomes,
safety, and pharmacokinetic proles will also be evaluated.
Discussion: ZEAL-1L will provide evidence whether Nira can prolong
disease control aer 1L chemotherapy when combined with Pembro and
evaluate its potential to decrease risk of occurrence or progression of CNS
metastasis in advanced NSCLC.
Conclusion: is ongoing study is registered at clinicaltrials.gov
(NCT04475939). Recruitment began November 2020.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts152
368
Snier dogs can identify lung cancer patients from breath and
urine samples
Charlotte Feil1; Frank Staib1; Martin R. Berger2; Thorsten Stein1;
Irene Schmidtmann3; Andreas Forster4; Carl C. Schimanski1
1Klinikum Darmstadt GmbH, Medizinische Klinik II, Darmstadt, Deutschland
2Deutsches Krebsforschungszentrum , Arbeitsgruppe Toxikologie und
Chemotherapie, Heidelberg, Deutschland
3Johannes Gutenberg-Universität, Institut für Medizinische Biometrie,
Epidemiologie und Informatik, Mainz, Deutschland
4Lungenzentrum Darmstadt, Darmstadt, Deutschland
Background: Lung cancer is the most common oncological cause of death
in the Western world. Even if early diagnosis is critical for successful treat-
ment, no eective screening methods exist. In several studies, dogs were
trained to discriminate cancer samples from controls by sniing volatile
organic compounds (VOC) as diagnostic biomarkers. In this study we
evaluated the abilities of a specically trained dog to distinguish samples
from lung cancer patients from matched healthy controls.
Methods: is single center, randomized, double-blind clinical trial with
432 patients was approved by the local ethics committee (FF20/2016).
Aer being conditioned with breath and urine samples of 150 controls
and 36 cancer patients comprising all stages, further 205 controls and 41
cancer patients were included for study phase. Two breath and urine sam-
ples were collected from each patient, and shock frozen. Only samples
from new subjects were presented to the dog.
Result: Using a combination of urine and breath samples, the dog cor-
rectly predicted 40 out of 41 cancer samples, leading to an overall detec-
tion rate of 97.6% (95% CI [87.1 %, 99.9 %]). Using urine samples only the
dog achieved a detection rate of 87.8% (95% CI [73.8 %, 95.9 %]). With
breath samples, the dog correctly identied cancer in 32 of 41 samples,
resulting in a detection rate of 78% (95% CI [62.4 %, 89.4 %]).
Discussion: Breath samples alone might be inferior for olfactory detec-
tion than urine samples. e combined method of both samples showed a
promising result as a non-invasive, riskless method. With dogs being indi-
viduals and therefore their use hard to standardize, further target com-
pounds and bias to olfactory detection need to be identied to develop an
electronic nose as a bionic approach.
Conclusion: Olfactory detection of lung cancer by specically trained
dogs is highly suggestive to be a simple and non-invasive tool to detect
lung cancer using VOC pointing to cancer growth in breath and urine
samples.
Disclosure Statement: e authors declare no conict of interest.
Published in BMC Cancer: https://doi.org/10.1186/s12885-021-08651-5
369
5th Nationwide Tumor-biological Testing Survey in Patients
with NSCLC in Germany – Current Results and Development
ofTesting Behavior since 2012
Helmut Ostermann1; Sonja Loges2
1LMU Klinikum, München, Deutschland
2Universitätsklinikum Mannheim, Department of Personalized Oncology,
Division of Personalized Medical Oncology (A420), DKFZ, , Mannheim,
Deutschland
Background: Targeted drug therapy following assessment of molecu-
lar alterations in tumor tissue has become standard-of-care in stage IV
NSCLC and recently as adjuvant treatment following resection in stage
IB-IIIA as well. Guidelines recommend the use of companion diagnostic
guided drug therapy from which many patients benet considerably. We
want to determine whether testing in Germany is performed as per guide-
line recommendations.
Methods: Experienced oncologists from dierent types of health care
institutions (certied lung cancer centers, university/ non-university
hospitals, oce-based physicians partly associated with network associ-
ations (nNGM, ZPM)) are asked to answer a questionnaire on the details
of testing. Data are analyzed by explorative analysis. e current results
are broken down by institution and compared with those from previous
surveys to analyze the development of testing behavior. In addition, this
year testing behavior in early stage NSCLC is evaluated.
Result: As previous surveys have shown, biomarker testing in Germany
has generally improved, however testing rates are biomarker dependent
and seem to reach partially a plateau at ~ 80% as indicated by 2019 rates
from EGFR 80%, PD-L1 81%, ALK 77%. In 2019 the greatest potential
for improvement was within the lung centers, where 18% of the patients
did not receive any type of biomarker analysis. Overall there is still poten-
tial for improvement in Germany in terms of the optimal use of therapy
options. ese data will again be examined in the new survey which is
currently ongoing. We will present the results and discuss the develop-
ment of testing in Germany from 2012 to 2021.
Conclusion: Despite guideline recommendations it appears that there is
still a signicant number of patients in whom tumor-biological testing is
not done and, therefore, access to optimal treatment may not be possible.
e results that will be presented will clarify whether important improve-
ments in the rate of testing have occurred within the last 2 years and put
that in a 10 year perspective.
Disclosure Statement: e authors declare the following: is study was support-
ed by Astra Zeneca
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 153
370
Tepotinib in patients (pts) with MET exon 14 (METex14)
skipping non-small cell lung cancer (NSCLC): Interim analysis
of VISION Cohorts A and C
Frank Griesinger1; Michael Thomas2; Niels Reinmuth3; Martin Wermke4;
Tobias Overbeck5; Jürgen Alt6; Sven Henschke7; Thomas Wehler8;
Sebastian Ochsenreither9; Marina Chiara Garassino10; Enriqueta Felip11;
Hiroshi Sakai12; Rolf Bruns13; Gordon Otto14; Andreas Johne14;
Paul K. Paik15,16
1Pius-Hospital, University Medicine Oldenburg, Department of Hematology
and Oncology, University Department Internal Medicine-Oncology, Oldenburg,
Deutschland
2Thoraxklinik, University Heidelberg and Translational Lung Research Center
Heidelberg (TLRC-H), The German Center for Lung Research (DZL), Heidelberg,
Deutschland
3Asklepios Lung Clinic, Munich-Gauting, Deutschland
4Technical University Dresden, NCT/UCC Early Clinical Trial Unit, Dresden,
Deutschland
5Clinic for Hematology and Medical Oncology, University Medical Center
Göttingen, Göttingen, Deutschland
6University Medical Center of the Johannes Gutenberg-University Mainz, Mainz,
Deutschland
7Saarland University Hospital, Homburg, Deutschland
8Evangelisches Krankenhaus Hamm GmbH, Hamm, Deutschland
9Charité Comprehensive Cancer Center, Berlin, Deutschland
10Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei
Tumori, Milan, Deutschland
11Department of Oncology, Vall dHebron Institute of Oncology (VHIO),
Barcelona, Spanien
12Department of Thoracic Oncology, Saitama Cancer Center, Saitama, Japan
13Department of Biostatistics, Merck Healthcare KGaA, Darmstadt, Deutschland
14Global Clinical Development, Merck Healthcare KGaA, Darmstadt, Deutschland
15Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center, New
York, USA
16Weill Cornell Medical College, New York, USA
Background: We report outcomes for tepotinib – a highly selective,
potent MET inhibitor – in patients (pts) with METex14 skipping in
VISION Cohorts A (primary analysis) and C (conrmatory), by prior
therapies. ese are relevant for clinical practice, given the approval by the
European Commission for tepotinib in pts with advanced NSCLC harbor-
ing METex14 skipping, previously treated with immunotherapy (IO) and/
or platinum-based chemotherapy (CT).
Methods: Pts with advanced/metastatic METex14 skipping NSCLC
received 500 mg (450 mg active moiety) tepotinib once daily. Safety
was assessed in all pts who received tepotinib, and ecacy in pts with
≥3 months’ follow-up (data cut-o: Feb 1, 2021). Primary endpoint was
objective response by IRC (RECIST 1.1).
Result: Of 275 pts evaluable for ecacy, 138 were previously treated
(2L+): median age 70.9 years (range, 41–89), 51% female, 40% smok-
ing history, and 42.0% enrolled in Europe. 86% of 2L+ pts had prior
platinum-based CT, 53% had prior IO (37% as monotherapy, 15% had
IO-CT). Objective response rate (ORR) was 44.2% (95% CI: 35.8, 52.9),
with median (m) DOR of 11.1 months (8.4, 18.5). Disease control rate
was 75.4% (67.3, 82.3), mPFS was 11.0 months (8.2, 12.4), and mOS was
19.9 months (15.8, 22.3). Ecacy was observed regardless of types of prior
therapies, including CT and/or IO. 137 pts were treatment-naïve (1L):
median age 74.6 years (range, 47–94), 50% female, 53% smoking history,
and 60.6% enrolled in Europe. ORR was 54.0% (45.3, 62.6) and mOS was
17.6 months (13.4, 29.7). Overall, pts with brain metastases at baseline
(51/275 [18.5%]) had systemic ORR of 52.9% (38.5, 67.1), and mDOR
of 9.0 months (5.6, ne). Treatment-related adverse events (TRAEs) were
mostly mild-moderate across therapy lines; Grade ≥3 TRAEs occurred in
33.1% of 1L pts and 25.9% 2L+ pts.
Conclusion: In VISION – the largest clinical trial of a MET inhibitor
in pts with METex14 skipping NSCLC – tepotinib demonstrated robust
and durable clinical activity in both 2L+ and 1L pts, and in pts with brain
metastases, with a tolerable safety prole.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
413
Survival outcomes in patients with sarcomatoid pleural
mesothelioma: a retrospective analysis from the last two
decades
Helge G. Bischo1; Rajiv Shah1; Miriam Blasi1; Jonas Kuon1; Petros
Christopolous1; Inn Chung1; Albrecht Stenzinger2; Mark Kriegsmann2;
Julia Glade2; Laura V. Klotz3; Martin E. Eichhorn3; Sabine Wessels1;
Thomas Muley4; Felix J.F. Herth5; Michael Thomas1
1Thoraxklinik, Thoraxonkologie, Heidelberg,
2Pathologisches Institut, Universität Heidelberg
3Thoraxklinik, Thoraxchirurgie
4Thoraxklinik, Translationale Forschung
5Thoraxklinik, Pneumologie und Beatmungsmedizin
Background: Sarcomatoid pleural mesothelioma (SM) is a rare histo-
logical sub-type of mesothelioma associated with poor overall survival
(OS). e therapeutical approach is based on systemic chemotherapy
(CT), despite a lower chemosensitivity as compared with the epithelioid
counterpart.
Methods: In this single-center, retrospective study we evaluated clinico-
pathological features, frontline treatment and survival outcomes of 63
patients with an ascertained pathological diagnosis of SM treated in our
center from 2000 until 2020.
Result: e median age was 71 years (range 45-88), 57 (90%) patients
were male. At the time of diagnosis, 52 (83%) patients had an Eastern
Cooperative Oncology Group Performance Status (ECOG PS) ≤ 1.
Twenty (32%) patients received best supportive care (BSC), 39 (62%)
received rst-line chemotherapy (CT), 3 (5%) trimodality treatment and
1 (2%) patient underwent surgery only. In the subgroup of patients with
rst-line CT, 26 (67%) were treated with a platinum-based doublet-CT,
while 13 (33%) received single agent CT (mono-CT).
Patients treated with CT had a median progression-free survival (PFS) of
2 months (95% condence interval (CI) 1.24-2.76) and a median OS of
7 months (95% CI 5.26-8.74). Compared with patients with mono-CT,
patients receiving doublet-CT had a longer median OS (3 months vs. 8
months, HR 0.42 [95% CI, 0.21-0.85], p=0.009). e median PFS was 3
months for patients receiving doublet-CT and 1 month for patients treated
with mono-CT (HR 0.87 [95% CI 0.43-1.74], p=0.63) e median OS of
patients receiving BSC was 2 months (95% CI 0.95-3.05). No signicant
dierence in OS was found when comparing mono-CT with BSC (3 vs. 2
months, HR 0.55 [95% CI, 0.26-1.17], p=0.082) and this was consistent in
the subgroup of patients aged ≥ 70 years (OS 3 vs. 2 months, HR 0.73 [95%
CI 0.3-1.75], p=0.440).
Conclusion: In patients with SM not eligible for frontline platinum-based
doublet-CT, treatment with single agent CT should be carefully evaluated,
since the survival benet is unclear.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts154
433
Clinical and pathological features and prognosis of non-small
cell lung cancer (NSCLC) patients with adenocarcinomas
without TTF1 and Napsin A expression
Franziska Kraus1; Georg Nilius2; Servet Bölükbas3; Imke Stöver4;
Andreas Koziorowski4; Florian Grabellus5
1Kliniken Essen-Mitte, Onkologie, Essen, Deutschland
2Kliniken Essen-Mitte, Pneumologie, Essen, Deutschland
3Klinken Essen-Mitte, Thoraxchirurgie, Essen, Deutschland
4Gemeinschaftspraxis für Strahlentherapie, Essen, Deutschland
5Zentrum für Pathologie Essen-Mitte, Essen, Deutschland
Background: TTF-1 helps to conrm a primary lung origin in 75-85%
of lung adenocarcinoma. But in the remaining patients (pts) TTF-1 is
not expressed. Clinical, pathological and molecular features about last
mentioned subgroup is lacking. Enteric dierentiation can occur in lung
adenocarcinoma and when this component exceeds 50%, the tumor is
classied as pulmonary adenocarcinoma with enteric dierentiation
(PAED).
Methods: Lung adenocarcinoma pts who were diagnosed from 01/2018
until 04/2021 were identied by review of the pts records. Only pts whose
tumors didn`t express TTF-1 and Napsin A were evaluated. Enteric ade-
nocarcinomas were conrmed by expression of CDX2, CK20 or MUC2.
Primary tumors of the gastrointestinal tract were excluded by PET-CT/
CT/endoscopy.
Result: A total of 53 pts (31 males (58.5%), 22 females (41.5%)) were
found. Median age was 68 ys (range: 54-83 ys). 24 pts were diagnosed
at a local stage, 29 pts had metastatic disease (stage IV). Tumors with
any PD-L1 expression were found in about 50 % of the pts. Median dis-
ease-free survival of 17 pts with surgical resection was 8 mths, median
progression-free survival of any stage IV pts (29) with rstline systemic
treatment was 3 mths. No dierence between chemotherapy and chemo-/
immunotherapy treatments were noticed (median PFS: 3 mths (range:
0-12) vs. 3 mths (range: 0-15). Furthermore, 15 pts suered from PAED.
Regarding molecular alterations in stage IV pts, a higher percentage of
KRAS mutations was found in PAED pts (37 % vs. 24.5 %).
Discussion: Compared to available data from TTF-1 positive patients
receiving rstline systemic treatment, the prognosis of TTF-1-negative
pts seems to be far poorer.
Conclusion: At present, this is the largest series of clinical and patho-
logical features of lung adenocarcinoma pts without TTF1- and Napsin
A-expression and particularly with enteric dierentiation.
Disclosure Statement: e authors declare no conict of interest.
462
Comparison of lung cancer-centersand non-centers: Regional
dierences in the patients characteristics and therapy of
bronchial carcinoma?
Johanna Oswald1; Tobias Robold1; Michael Gerken2,3; Luisa Horn1;
Konstantin Fitilidis1; Monika Klinkhammer-Schalke2,3;
Hans-Stefan Hofmann1
1University Hospital Regensburg, Department of Thoracic Surgery, Regensburg,
Deutschland
2Institute for Quality Management and Health Services Research, University of
Regensburg, Tumour Centre, Regensburg, Deutschland
3Bavarian Health and Food Safety Authority, Bavarian Cancer Registry, Regional
Centre Regensburg, Deutschland
Background: e “Further development of oncological care structures
and quality assurance” is part of the National Cancer Plan of the Federal
Ministry of Health. e present work is intended to contribute to a trans-
parent presentation of current care by means of a regional comparison of
patient and treatment structures.
Methods: In a retrospective study based on data from a population-based,
clinical cancer registry from the Lower Bavaria/Upper Palatinate region,
the aim is to investigate whether local, oncological structure requirements
show an inuence on therapy and patient outcome. For this purpose,
patient data from the years 2015-2018 from lung cancer centres (group1,
corresponding to the structural specications of the German Cancer
Society) were compared with data from clinics not certied as lung cancer
centres (group 2).
Result: Data were collected from 3952 patients; aer exclusion, 3686
remained for the analyses. e distribution of the analysed patients
in the two comparison groups is 55% in group 1 and 45% in group 2.
Unadjusted, there is a signicant survival advantage for patients in lung
centres compared to non-certied hospitals, which also remains in the
multivariable model. If the stage distribution is taken into account, a sig-
nicant survival time advantage is shown in stages I and II for group 1.
For stages III and IV, no signicant dierence in survival compared to the
comparison group can be observed.
Discussion: e limitations of a retrospective cohort-study were ade-
quately addressed with risk-adjustment by multivariable regression
analyses.
Conclusion: e data already available show an advantage in overall sur-
vival for treatment in lung cancer centres, but at the same time also a less
favourable distribution of risk factors in the comparison group. e rea-
sons for the signicant dierences must be worked out in further analyses,
considering additional factors.
Disclosure Statement: e authors declare no conict of interest.
482
The peripheral T-cell receptor repertoire in metastatic non-
small-cell lung cancer patients receiving rst- or second-line
immunotherapy and the inuence of CMV seropositivity
Mariam Elshiaty1,2; Fabienne Lusky1,2; Farastuk Bozorgmehr1,2;
Isabel Poschke3; Hannah Schindler1,2; Arlou K. Angeles2,4; Jonas Kuon1;
Rajiv Shah1; Simon J. Ogrodnik2,4; Lena Gaissmaier1,2; Marc A. Schneider2,5;
Daniel Kazdal2,6; Michael Allgäuer6; Michael Meister2,5; Thomas Muley2,5;
Felix J. Herth2,7; Hauke Winter2,8; Florian Eichhorn2,5,8; Paul Schnitzler9;
Albrecht Stenzinger2,6; Holger Sültmann2,4; Michael Thomas1,2;
Petros Christopoulos1,2
1Thoraxklinik at Heidelberg University Hospital and National Center for Tumor
Diseases, Department of Thoracic Oncology, Heidelberg, Deutschland
2Translational Lung Research Center Heidelberg (TLRC), German Center for Lung
Research (DZL), Heidelberg, Deutschland
3Deutsches Krebsforschungszentrum (DKFZ) Heidelberg, Division of Molecular
Oncology of Gastrointestinal Tumors, Heidelberg, Deutschland
4Deutsches Krebsforschungszentrum (DKFZ) Heidelberg, Division of Cancer
Genome Research, Heidelberg, Deutschland
5Thoraxklinik at Heidelberg University Hospital, Translational Research Unit,
Heidelberg, Deutschland
6Institute of Pathology Heidelberg University, Heidelberg, Deutschland
7Thoraxklinik at Heidelberg University Hospital and National Center for Tumor
Diseases, Department of Pneumology and Critical Care Medicine, Heidelberg,
Deutschland
8Thoraxklinik at Heidelberg University Hospital and National Center forTumor
Diseases, Department of Thoracic Surgery, Heidelberg, Deutschland
9Center for Infectious Diseases, University Hospital of Heidelberg, Department
of Virology
Background: Metastatic non-small-cell lung cancer (NSCLC) patients
oen receive immunotherapy (IO) as rst- (1L) or second-line (2L) treat-
ment, but the majority do not respond, and reliable biomarkers for IO
benet are lacking.
Methods: We retrospectively analyzed baseline blood samples of
IO-treated stage IV NSCLC patients, who either experienced rapid pro-
gression (RP, progression-free survival [PFS] < 6 months), long-term ben-
et (LR, [PFS] >12 months), or an intermediate course (IR, [PFS] 6-12
months). e patients were divided in 3 cohorts: patients receiving IO as
1L treatment (1L-IO, n=45), patients receiving IO as 2L treatment (2L-
IO, n=36) and patients receiving IO combined with chemotherapy as 1L
treatment (1L-CTxIO, n=38). Age-matched healthy donors (n=20) were
included as controls. e T cell receptor (TCR) repertoire was analyzed
by TCRβ next-generation sequencing using the immunoSEQ platform
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 155
(Adaptive Biotechnologies). Furthermore, available serum samples
(n=86) were tested for CMV seropositivity.
Result: No signicant dierences in the TCRβ clonality of baseline blood
samples were noted between the LR and RP subsets of each cohort (1L-
IO, 2L-IO, 1L-CTxIO). 2L-IO patients showed a higher clonality than
both the control and 1L-IO cohorts (0.086 vs 0.048 and vs 0.046, p <0.05).
Based on available serum samples, CMV seropositivity was 62% (53/86)
and correlated positively with clonality (r=0.661, p <0.001), which was
signicantly higher in CMV positive samples (0.099 vs 0.026, p <0.001).
Discussion: In NSCLC, the TCRβ repertoire clonality in peripheral blood
increases with previous treatments, but baseline values are not predictive
of response to IO or CTxIO. CMV seropositivity is common (>50%) in
NSCLC and appears to inuence TCRβ clonality more than previous
treatments.
Conclusion: Baseline TCRβ repertoire clonality alone is not a predictive
biomarker for immunotherapy outcome in NSCLC. Ongoing work is eval-
uating the association with tumor characteristics, as well as longitudinal
changes and their potential relationship with the clinical course.
Disclosure Statement: e authors declare the following: P.C. declares research
funding from AstraZeneca, Novartis, Roche, Takeda, and advisory board/lecture/
educational fees from AstraZeneca, Boehringer Ingelheim, Chugai, Kite, Novartis,
Pzer, Roche, and Takeda. M.E. declares no conict of interest.
500
Upfront and repeated stereotactic radiosurgery in patients
with brain metastases from NSCLC – Clinical outcome and
validation of prognostic scores
Anna Krämer1; Sebastian Adeberg1; Dorothea Kronsteiner2; Laila König1;
Fabian Schunn1; Farastuk Bozorgmehr3; Petros Christopoulos3;
Tanja Eichkorn1; Stefan Rieken4; Jürgen Peter Debus1; Rami El Shae1,4
1RadioOnkologie und Strahlentherapie, Universitätsklinikum Heidelberg,
Heidelberg, Deutschland
2Institut für Medizinische Biometrie und Informatik, Universitätsklinikum
Heidelberg, Heidelberg, Deutschland
3Innere Medizin, Thoraxklinik-Heidelberg gGmbH, Heidelberg, Deutschland
4Klinik und Poliklinik für Strahlentherapie und Radioonkologie ,
Universitätsmedizin Göttingen , Göttingen, Deutschland
Background: Approximately 40% of NSCLC patients develop brain
metastases (BM) during the course of their disease. Stereotactic radiosur-
gery (SRS) instead of whole-brain radiotherapy (WBRT) is increasingly
administered as an upfront treatment to patients with one or multiple
BM. We present outcomes and validation of prognostic scores for a large
cohort of patients with BM from NSCLC treated with upfront SRS.
Methods: We retrospectively analyzed 199 patients with a total of 268
SRS courses for 539 brain metastases. Median patient age was 63 years
(IQR: 56-69) and the median initial number of metastases per patient was
2 (IQR: 1-4, Range: 1-17). 54 (27,2%) patients received more than one SRS
course. SRS was delivered at a dose of 20 Gy. For larger BM, dose reduc-
tion to 18 Gy or hypofractionated SRS in 6 fractions was applied. In cases
of intracranial progression, repeated SRS was delivered when clinically
feasible. We analyzed the BMV-, the RPA-, the GPA- and the lung-mol
GPA score. Cox proportional hazards models with univariate and multi-
variate analyses were tted for overall survival (OS) and intracranial pro-
gression-free survival (icPFS).
Result: 64 patients died, seven of them of neurological causes. 38 patients
(19,3%) required a salvage WBRT due to intracranial progression. Median
OS was 38,8 months (IQR: 6-NA). In univariate analysis as well as mul-
tivariate analysis, the Karnofsky performance scale index (KPI) ≥ 90%
(p=0,012 and p=0,041) remained as independent prognostic factor for
longer OS. All four prognostic scoring indices could be validated for OS
assessment (BMV p=0,007; RPA p=0,026; GPA p=0,003; lung-mol GPA
p=0,05).
Discussion/Conclusion: In this large cohort of NSCLC patients with
BM treated with upfront and repeated SRS, OS was markedly favourable,
in comparison to literature. Only few patients required salvage WBRT
or died of neurological causes. Upfront SRS is an eective treatment
approach in those patients and can decidedly reduce the impact of BM on
overall prognosis. Furthermore, the analysed scores are useful prognostic
tools for OS prediction.
Disclosure Statement: e authors declare no conict of interest.
Lung Cancer
510
A multi-methods preclinical platform to inform clinical
decision making in lung cancer patients with uncommon
driver mutations - A project from the national Network
Genomic Medicine.
Melanie Janning1,2,3,4, Martin Ziegler1,2,4, Corinna Albers-Leischner3,
LorenaSalgueiro1,2,4, Christina Alidousty5, Felix C Saalfeld6,
SebastianMerker7, Carina Wenzel8, Daniel Stange7,9, Jürgen Wolf10,
Reinhard Büttner5, Christian Brandts11, Martin Wermke6, Sonja Loges1,2,3,4
1Division of Personalized Medical Oncology (A420), Deutsches
Krebsforschungszentrum, Heidelberg, Deutschland
2Department of Personalized Oncology , University Hospital Mannheim,
Medical Faculty Mannheim, University of Heidelberg, Mannheim, Deutschland
3Department of Oncology, Hematology and Bone Marrow Transplantation with
section Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg,
Deutschland
4DKFZ-Hector Institute at the University Hospital Mannheim, Mannheim,
Deutschland
5Institute of Pathology, University Hospital Cologne, Cologne, Deutschland
6Clinic for Internal Medicine I, Medical Faculty and University Hospital Carl
Gustav Carus, Technische Universität Dresden, Dresden, Deutschland
7National Center for Tumor Diseases (NCT) Dresden, German Cancer Research
Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University
Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany;
Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany
8Institute of Pathology, Medical Faculty and University Hospital Carl Gustav
Carus Dresden
9Department of Visceral, Thoracic and Vascular Surgery, Medical Faculty and
University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden,
Deutschland
10Department of Internal Medicine, Center for Integrated Oncology, University
Hospital Cologne, Cologne, Deutschland
11Department of Medicine, Hematology/Oncology, University Hospital
Frankfurt, Goethe University, Frankfurt, Deutschland
Background: Increased use of next generations sequencing revealed a
substantial number of patients with uncommon variants of mutations.
For lung cancer patients we estimated, that ~ 2000 patients are newly
diagnosed per year with such uncommon variants in Germany. Little is
known about possible driver function and therapeutic susceptibilities of
individual mutations or their combinations. Because patients with driver
mutations benet more from targeted therapies than chemotherapies,
there is an unmet clinical need to determine the clinical implications of
carrying such variants. Here we present a novel multicenter platform of
the national Network Genomic Medicine Lung Cancer (nNGM) with the
aim to generate preclinical real-time evidence on uncommon mutations
to support clinical decision making.
Methods: In-silico prediction modelling together with cell-based assays
such as the IL3-dependent Ba/F3 system will be used for prediction of
driver function. Inhibitory potency for dierent drugs will be determined
using protein-ligand binding and viability assays. Patient-derived cancer
organoids (PDO) are continuously established to perform drug screens
and long term exposure of cultures will be analyzed towards resistance
development.
Result: e platform will be available for all nNGM participating cen-
ters. Aer notication of the mutation by the treating physician, possi-
ble driver activity and sensitivity analyses based on in-silico and in-vitro
assays will be available within 4 weeks. is information will be fed into
the nNGM digital annotation platform MURIPEDIA and be available to
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts156
inform nNGM MTBs. Correlation of clinical response with predicted sen-
sitivity proles will inform a self-learning, evidence-generating system. A
biobank of PDO is being generated and a drug plate of selected TKIs is
being constructed.
Discussion: We will evaluate to what extend pre-clinical data can be used
to inform clinical decision making
Conclusion: e platform in combination with collection of clinical fol-
low-up will generate evidence for treatment of uncommon mutations.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
518
Proteasomal processing alterations as a novel mechanism of
immune escape in NSCLC straties patients for response to
immune checkpoint blockade
Michael Wessolly1; Marcel Wiesweg2; Sabrina Borchert1; Hendrik Beckert3;
Susann Stephan-Falkenau4; Elena Mairinger1; Jens Kollmeier5;
Clemens Aigner6; Christian Taube3; Jeremias Wohlschlaeger7;
Thorsten Bauer5; Thomas Mairinger4; Kurt Werner Schmid1;
Martin Schuler2; Henning Reis1; Fabian Dominik Mairinger1
1Institute of Pathology, University Hospital Essen, Deutschland
2Clinical for internal medicine (tumor research), West German Cancer Center,
University Hospital Essen, Deutschland
3Department of Pulmonary Medicine, University Hospital Essen, Deutschland
4Department of Tissue Diagnostics, Helios Klinikum Emil von Behring,
Deutschland
5Lungenklinik Heckeshorn, Helios Klinikum Emil von Behring, Deutschland
6Department for Thoracic Surgery, University Hospital Essen, Deutschland
7Department of Pathology, Diakonissenkrankenhaus Flensburg, Deutschland
Background: Immunotherapy has recently become a game changer in
the treatment of treatment-naive and oncogenic-driver wild type NSCLC,
with immune checkpoint inhibitors (ICIs) frequently used. Although ICIs
are an eective therapy, the main problem of primary resistance remains.
Not much attention, however, has been paid to immunogenic quality of
tumor neoantigens. In previous work, we identied altered epitope pro-
cessing as an important mechanism for tumor immune escape.
Methods: FFPE samples from patients with treatment-naïve advanced
NSCLC that received 1L anti-PD-1 ICI therapy were analyzed for both
WES and digital gene expression analysis (NanoString nCounter analy-
sis). For prediction of proteasomal cleavage, the machine learning tool
NetChop 3.1 was used. Results were introduced to an explorative data
analysis for clinicopathological and follow-up data, resulting in a compar-
ative patient stratication for ICI treatment.
Results: Patients showing processing escapes revealed a signicantly
shortened OS aer ICI treatment (p=0.008, HR: 2.85, 95% CI: 1.27-6.41).
e one-year OS rate diers from 26.4% to 63.1% (95% CI: 13.8-50.5 vs.
45.5-87.5). Moreover, a signicantly shortened time-to-treatment-failure
(TTF) time has been revealed (p=0.002, HR: 2.78, 95% CI: 1.41-5.46).
e one-year TTF rate diers from 15.7% to 60.2% (95% CI: 7.1-34.7 vs.
42.8-84.7).
Discussion: In line with our previous ndings from real-world data based
on targeted amplicon-based sequencing, we can validate the eect of a
processing escape phenotype on patient survival and outcomes aer ICI.
e determination of processing escapes in the subset of expressed genes
revealed a clear trend for both shortened TTF and OS aer ICB in the
processing escape group.
Conclusion: We have demonstrated the negative impact of mutations
leading to non-immunogenic neoantigens on patients response to ICI
therapy. is should be considered for further adaptions of diagnostic
processes to overcome therapy resistance.
Disclosure Statement: e authors declare no conict of interest.
551
CRP kinetics as an early predictive biomarker for response to
anti-PD-L1 therapy in advanced NSCLC
Jonas Saal1; Niklas Klümper2; Fiamma Berner3; Christa Lichtensteiger3;
Annkristin Heine1; Franz-Georg Bauernfeind1; Jörg Ellinger2;
Peter Brossart1; Manuel Ritter2; Michael Hölzel2; Lukas Flatz3; Tobias Bald4
1Medizinische Klinik 3 für Hämatologie und Onkologie, Universitätsklinikum
Bonn, Bonn, Deutschland
2Klinik für Urologie, Universitätsklinikum Bonn, Bonn, Deutschland
3Klinik für Dermatologie, Universitätsklinikum Tübingen, Tübingen ,
Deutschland
4Institut für experimentelle Onkologie, Universitätsklinikum Bonn, Bonn,
Deutschland
Background: Predictive biomarkers for response to immune-check-
point blockade (ICB) are lacking. Recently C-reactive protein (CRP) are
kinetics were associated with response to ICB in patients suering from
renal cell carcinoma (1). Here we investigated, if CRP are kinetics can
predict response and outcome in ICB-treated non-small-cell lung cancer
(NSCLC) patients.
Methods: A prospective cohort of 107 patients with advanced stage
NSCLC treated with ICB alone (79%) or in combination with chemother-
apy (21%) was analyzed for CRP kinetics and outcome. e results were
veried in a retrospective cohort including 105 patients. Patients were
classied by CRP kinetics as are-responders (increase in CRP levels to at
least 2x baseline with subsequent drop below baseline within 3 months),
responders (CRP decreasing at least 30% below baseline within 3 months)
and non-responders (others).
Results: CRP are correlated with improved OS when compared to
responders and non-responders (34.0 vs 17.9 vs 6.6 months, HR 0.26) and
PFS (16.8 vs 7.9 vs 2.3 months, HR when compared to non-responders
0.32). Overall response rate (ORR) in rst staging was 95.7% in are-re-
sponders, 66.7 % in responders and 40.0% in non-responders. We could
verify those results in a retrospective cohort (HR when compared to
non-responders for OS 0.49 and for PFS 0.44).
Discussion: Our data provide the rst evidences that early CRP kinet-
ics correlate with response and survival in ICB-treated NSCLC patients.
Hence CRP values are widely available, easy to obtain and can be evalu-
ated as early as 4-6 weeks aer start of therapy CRP-kinetics could provide
a valuable on-treatment biomarker for response in NSCLC patients.
Conclusion: CRP are kinetics can predict response and survival in ICB
treated NSCLC.
Indication of source:
1. Fukuda et al. Impact of C-reactive protein are-response on oncological
outcomes in patients with metastatic renal cell carcinoma treated with
nivolumab. J Immunother Cancer. 2021;9(2).
Disclosure Statement: e authors declare no conict of interest
606
Safety and ecacy of simultaneously performed radiotherapy
in patients with small-cell lung cancer undergoing
atezolizumab treatment
Julia Galuba1; Imke Stöver2; Andreas Koziorowski2; Servet Bölükbas3;
Georg Nilius4; Daniel Christoph1,1
1Department of Medical Oncology, Evang. Kliniken Essen-Mitte, Essen,
Deutschland
2Practice for Radio-Oncology Essen, Essen, Deutschland
3Department of Thoracic Surgery, Evang. Kliniken Essen-Mitte, Essen,
Deutschland
4Department of Pneumology, Evang. Kliniken Essen-Mitte, University Witten-
Herdecke, Essen, Deutschland
Background: In 2019 atezolizumab was approved for extended disease
small cell lung cancer (SCLC) in combination with cytotoxic chemother-
apy. In the clinical trial IMpower133 only 22 out of 201 patients (pts)
received prophylactic cranial radiotherapy (PCI) during their treatment
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 157
with atezolizumab. To our knowledge, no other clinical studies have
reported ecacy or safety regarding the combination of radiotherapy
(PCI, whole brain radiotherapy or consolidating thoracic radiother-
apy (CTR)) with atezolizumab as single agent or in combination with
chemotherapy.
Methods: We performed a retrospective data analysis of all pts with SCLC
who were treated at the Department of Medical Oncology, Evang. Kliniken
Essen-Mitte from January 2019 until December 2021. Pts with combined
chemo-/immunotherapy as induction treatment or with immunotherapy
as maintenance were compared to those without any immunotherapy
receiving similar radiotherapies, including pulmonary function (if possi-
ble), Odds-Ratio for adverse events, progression-free-survival (PFS) and
overall-survival.
Result: 48 SCLC pts underwent cranial and/or thoracal irradiation.
Atezolizumab was administered to 21 of them. A total of 24 pts received
combined chemo-/immunotherapy without any radiotherapy. ere were
no severe AEs in pts with cranial radiotherapy regardless of simultaneous
administration of atezolizumab. In pts with CTR, there was no signicant
dierence in grade I to III AEs. A statistical trend towards an improved
median PFS was found in patients with CTR. ere is preliminary evi-
dence for no deterioration of pulmonary function for pts receiving
simultaneous CTR and atezolizumab compared to pts with CTR without
atezolizumab.
Discussion: Although it was only a small retrospective study, there is no
evidence for additional toxicity for patients undergoing simultaneous
immunotherapy and radiotherapy. Further prospective studies are needed.
Conclusion: e addition of simultaneous radiotherapy to immunother-
apy seems not to be associated with increased toxicity in SCLC patients.
Disclosure Statement: e authors declare the following: Daniel C. Christoph
reports personal fees, non-nancial support and other from AstraZeneca, Bayer,
Boehringer-Ingelheim, Bristol-Myers Squibb, Chugai, MSD Sharp & Dohme,
Novartis, Pzer, Roche, and Takeda.
694
Curative treatment in EGFR mt+ NSCLC stage III by induction
TKI-chemotherapy combination: Feasibility and outcome
in 10 cases
Frank Griesinger1; Julia Roeper1; Kay Willborn2; Regina Prenzel2;
Douglas Scriba2; Martin Sebastian3
1Universitätsklinik Innere Medizin-Onkologie Universität Oldenburg, Pius
Hospital Oldenburg, Oldenburg, Deutschland
2Pius Hospital Oldenburg, Oldenburg
3Universitätsklinikum Frankfurt, Frankfurt
Background: EGFR TKI’s are a mainstay in the treatment of metastatic
NSCLC with EGFR mt+, however their use in the curative setting is not
yet standard of care. Recently, combination of TKI and chemotherapy
has been shown to improve ORR, PFS and OS in the metastatic setting.
Induction therapy with chemotherapy with or without radiotherapy is an
established approach in stages II and III, however no data exist for induc-
tion therapy with TKI and chemotherapy in EGFR mt+ NSCLC. Here
we describe the outcome of 10 pts with EGFR mt+ NSCLC, all stage III,
treated with 1st and 3rd gen TKI in combination with chemotherapy as
induction therapy.
Methods: 10/10 pts had adenocarcinoma, 6 with EGFR exon 19 and 4 with
EGFR L858R. Pts received erlotinib (n=2), getinib (n=5) or osimertinib
(n=3) for 10 days followed by TKI in combination with chemotherapy
(docetaxel/cisplatin (n=5), paclitaxel/carboplatin (n=5)) for 3 cycles.
Results: 7/10 pts achieved radiologic PR aer 2 cycles, all tumors were
R0 resected. pCR was achieved in the primary tumor in 2/10, 5 pts did
not achieve pCR or MPR in the primary tumor. In the mediastinal lymph
nodes, MPR was achieved in 6/10 pts (1 pCR). 2 pts achieving pCR in the
primary tumor, 5 pts relapsed at 8 to 17 (median 12) months, 3/5 with
CNS as 1st relapse site and 2/5 with other sites. 3/10 pts have just started
therapy. With a median follow up of 46 months (13-68), 6 patients are
alive at 2+, 2+, 2+, 13+, 44+, 67+ months and one patient died in CR of
secondary cancer at 51 months. Median OS of the 10 pts was 51 months
and median PFS was 17 months.
Conclusion: In conclusion 1st and 3rd gen TKI-chemotherapy induction
in EGFR mt+ NSCLC is feasible, leads to high MPR rates in mediastinal
lymph nodes and lower pathologic response rates in the primary tumors.
pCR in the primary tumor may predict better outcome. As CNS is the
most frequent site of relapse this site might be of special interest in further
induction studies on EGFR mt+ NSCLC.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
706
Adherence to treatment recommendations from
multidisciplinary tumor boards
Julia Roeper1; Alice Blanksma1; Louis Kathmann1; Lena Ansmann2;
Frank Griesinger1
1Universitätsklinik Innere Medizin-Onkologie Universität Oldenburg, Pius
Hospital Oldenburg, Oldenburg, Deutschland
2Universität Oldenburg, Department für Versorgungsforschung,
Organisationsbezogene Versorgungsforschung, Oldenburg, Deutschland
Introduction: Lung cancer centers are responsible for coordinating the
care of lung cancer patients in a region and to diagnose and treat them
according to the latest evidence-based knowledge. In the tumor board an
individual treatment plan is discussed and treatment recommendations
are given. erefore, we investigate: 1.) how are the recommendations
from tumor boards being adhered to; 2.) which factors determine the
adherence of tumor board recommendations and 3.) what is the rela-
tionship between the adherence of tumor board recommendations and
patient outcomes in terms of OS?
Methods: Data from 1784 newly-diagnosed patients with lung cancer dis-
cussed in tumor boards in one certied lung cancer center in Northern
Germany between 2014 and 2018 were documented and evaluated accord-
ing to the adherence to tumor board recommendations. An analysis of the
rst 386 cases analyzed will be presented. Data was analyzed descriptively.
Results: Median age of the 386 patients was 66 years (26-91 yrs) and 64%
(n=247/386) of them were male. Most of the patients had an ECOG of 0
or 1 (78%; n=301/386) and 87% of them were current or ex heavy smoker
(n=335/386). In 79% (n=304/386) of patients, the treatment recommen-
dations from the multidisciplinary tumor boards were completely adhered
to. ere were dierent reasons for non-adherence, e.g. patient’s wish,
patient characteristics and death before starting therapy. e median OS
for the 386 patients was 13 months. Patients with a complete adherence
to the multidisciplinary tumor board recommendation had an OS of 16
months (n=304) compared to 5 months (n=41) for patients with a partial
adherence compared to 1 months (n=33) for patients with a non-adherent
treatment (p<0.001).
Conclusion: Preliminary results give a hint to the fact that patients with
an adherent treatment aer rst diagnosis had a longer overall survival
than patients with another therapy. More cases will be presented at the
meeting using a multivariate analysis which includes patient character-
istics and healthcare organizations that took over further treatment as
predictors.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts158
707
Real-world analysis of treatment and outcome for large-cell
neuroendocrine lung carcinoma
David Fisch1; Farastuk Bozorgmehr1; Daniel Kazdal2; Jonas Kuon3;
Laura Klotz4; Rajiv Shah1; Florian Eichhorn4; Mark Kriegsmann2;
Marc Schneider5; Albrecht Stenzinger2; Thomas Muley5; Helge G. Bischo1;
Michael Thomas1; Petros Christopoulos1
1Thoraxklinik Heidelberg , Abteilung für Thoraxonkologie, Heidelberg,
Deutschland
2Pathologisches Institut - Universitätsklinikum Heidelberg, Allgemeine
Pathologie und Pathologische Anatomie, Heidelberg,
3Thoraxklinik Heidelberg , Thoraxchirurgie, Heidelberg, Deutschland
4Thoraxklinik Heidelberg , Abteilung für Thoraxchirurgie, Heidelberg,
Deutschland
5TLRCTranslational Lung Research Center am Universitätsklinikum Heidelberg,
Heidelberg, Deutschland
Background: Large-cell neuroendocrine lung carcinoma (LCNEC) is a
rare pulmonary neoplasm with poor prognosis and limited therapeutic
options.
Methods: We retrospectively analyzed all patients with metastatic LCNEC
in the records of a large German academic center since 2010.
Result: 191 patients were identied with a predominance of male (68%)
smokers (92%) and a median age of 65 years. e single most import-
ant factor associated with outcome was the type of systemic treatment,
with a median overall survival (OS) of 26 months in case of immuno-
therapy (n=13), 9 months for other patients with rst-line platinum dou-
blets (n=129), and 4 months with non-platinum chemotherapies (n=17,
p<0.01). A lower baseline serum LDH (hazard ratio [HR] 0.54, p=0.008)
and fewer initial metastatic sites (HR 0.52, p=0.006) were independently
associated with longer OS, while the platinum drug type (cisplatin vs. car-
boplatin) and cytotoxic partner (etoposide vs. paclitaxel), patients’ smok-
ing status and baseline levels of tumor markers (NSE, CYFRA 21-1, CEA)
did not matter. 12% (23/191) of patients forewent systemic treatment,
mainly due to tumor-related clinical deterioration (n=13), while patient
refusal of therapy (n=5) and severe concomitant illness (n=5) were less
frequent. e attrition between successive treatment lines was approxi-
mately 50% and similar for platinum-based vs. other therapies, but higher
in case of a worse initial ECOG status or higher serum LDH (p<0.05). 19%
(36/191) of patients had secondary stage IV disease and showed fewer
metastatic sites, better ECOG status and longer OS (median 12.6 vs. 8.7
months, p=0.030).
Discussion: Highly active systemic therapies, especially immunotherapy
and platinum doublets, are essential for outcome in LCNEC and inuence
OS stronger than other disease parameters. e attrition between chemo-
therapy lines is ca. 50%. Patients with secondary metastatic disease have a
more favorable clinical phenotype and longer survival.
Conclusion: LCNEC shows considerable clinical heterogeneity, which
could be used for individualized management
Disclosure Statement: e authors declare no conict of interest.
712
Evaluation of the prognostic marker of PD-L1 expression after
combined radiochemotherapy in patients with non-small cell
lung cancer (NSCLC) stage III
Jan Wagner1; Julia Roeper1; Kay Willborn2; Frank Griesinger1
1Universitätsklinik Innere Medizin-Onkologie Universität Oldenburg,
PiusHospital Oldenburg, Oldenburg, Deutschland
2Pius Hospital Oldenburg
Background: e PACIFIC study showed that pts with locally advanced,
unresectable NSCLC aer radio-chemotherapy derived a benet in PFS
and OS when treated with durvalumab. In a post hoc analysis this eect was
limited to pts with a PD-L1 of >1%. In contrast, in pts with PD-L1 of <1%,
no benet was seen partly due to the fact that the outcome in the control
arm was surprisingly favorable. us, it could be speculated that lack of
PD-L1 expression confers a favorable outcome aer radio-chemotherapy
in stage III NSCLC. To address the question, whether the prolonged OS in
the control group with lack of PD-L1 expression was reproducible we ana-
lyzed the PFS and OS in a group of 99 pts with stage III NSCLC homoge-
neously treated with radio-chemotherapy similar as in the PACIFIC trial
and not progressing aer radio-chemotherapy.
Methods: Clinical data, tumor characteristics and outcome were system-
atically captured from the data base of the certied lung cancer center
Oldenburg, including the PD-L1-score. In cases, where the PD-L1 expres-
sion had not been evaluated, the available tissues samples were reanalyzed
for PD-L1 expression by Hematopathology Hamburg, aer informed con-
sent of the surviving pts had been obtained. For statistical analyses, log
rank test as well as multivariate analyses were performed.
Results: e study showed that the expression of PD-L1 is independent
from gender and histology. e median OS of the pts with an expression
of PD-L1 <1% was 20 months (KI 10.5 – 29.5) and with an expression ≥1%
28 months (KI 16.5 – 39.3), however this dierence was not statistically
signicant with a p-value of 0.734. e median PFS of pts with an expres-
sion of PD-L1 <1% was 9 months (KI 6.4 – 11.6) and with an expression
≥1% 12 months (KI 9.8 – 14.2), also not being statistically signicant with
a p-value of 0.112. e blood parameters serum CRP, albumin and CRP/
albumin-ratio had no signicant impact on OS.
Conclusion: is study showed that the assumption that lack of PD-L1
expression confers a favorable prognosis aer radio-chemotherapy vs.
PD-L1 expression >1% was not conrmed in our patient cohort.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
728
Predictive factors in the therapy of NSCLC with
pembrolizumab
Sonja Traubeck1; Amanda Tufman1; Diego Kaumann-Guerrero1
1LMU University Hospital Munich, Department of Internal Medicine
V - Pulmonology, Munich, Deutschland
Background: Pembrolizumab is used both as monotherapy and com-
bination therapy in the treatment of NSCLC. ough it has proven
eective in many patients, there is a lack of clinical parameters cor-
relating with therapy outcome. is study investigated immunologic
and patient- specic parameters among a cohort of patients treated with
pembrolizumab.
Methods: We analyzed a retrospective cohort of 115 NSCLC patients
diagnosed and treated with pembrolizumab monotherapy or IO-chemo
combination at a tertiary care lung cancer center between 2015 and 2021.
Patient data was extracted from electronic and paper-based clinical les.
Result: Our total cohort was predominantly male (58.8%), the mean age
was 64.8 years and 60.5% had adenocarcinoma histology. Patients who
underwent pembrolizumab monotherapy proved signicantly older, har-
bored higher PD-L1 expression, and showed poorer performance status.
Pre-therapeutic neutrophile and lymphocyte counts as well as neutro-
phile-to-lymphocyte ratio signicantly predicted PFS in patients with
monotherapy, but not in combination treatment. Furthermore, elevated
CRP, neutrophile counts, NLR, eosinophile-to-lymphocyte ratio, throm-
bocyte-to-lymphocyte ratio, and the systemic inammation index were
signicantly associated with poor OS in patients with monotherapy as
well as those treated with IO combination.
Discussion: New reliable predictive factors are needed to characterize
NSCLC patients who benet from pembrolizumab treatment. e results
of our analysis indicate that baseline characteristics as well as standard
blood counts could be promising markers. However, prospective cohorts
are needed to conrm our hypotheses generating results.
Conclusion: Clinical patient characteristics as well as routinely obtained
pre-therapeutic markers and scores can predict prognosis of NSCLC
patients treated with pembrolizumab. is might be a helpful and cost-ef-
fective tool to guide patient treatment.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 159
760
The expression of genetic variants of cytochrome CYP1A1
(m1, m2 and m4) and their association with increased risk of
lung cancer
Darko Katalinic1; Ivan Aleric1; Aleksandar Vcev1; Lilly Soerensen2
1Faculty of Dental Medicine and Health and Faculty of Medicine, J.J. Strossmayer
University, Osijek, Kroatien
2Department of Cancer Medicine, Oslo, Norwegen
Background: e cytochrome P450 superfamily metabolic enzymes
(P450) could have a possible role in lung cancer susceptibility. erefore,
it is important to dene the expression prole of P450 and to establish
their prognostic signicance in subjects with lung cancer. e aim of the
study was to assess the role of CYP1A1 genotype and the possible associ-
ation with the risk of lung cancer development.
Methods: e study was performed among 359 subjects (69% males and
31% females; mean age of 59.96±18.24 years) with diagnosis of stage IV
small-cell (24.6% of patients) and non-small cell lung cancer (75.4% of
patients) compared to 167 healthy subjects (72% males and 28% females;
mean age of 69.96±11.74 years). e distribution of polymorphisms
CYP1A1(m1), CYP1A1(m2) and CYP1A1(m4) were detected using
quantitative real-time polymerase chain reaction restriction fragmenth
length polymorphisms assay (qRT-PCR-RFLP).
Result: Distribution of genetic variants CYP1A1(m1) and CYP1A1(m2)
were found to be statistically signicant (p<0.001) (40.1% and 31.4%
among lung cancer subjects compared to 31.2% and 19.6% amoung
control subjects). No polymorphic CYP1A1 (m4) genetic varinats were
detected among all subjects. Statistical analysis showed signicant risk
limited to squamos cell lung carcinoma in subjects carring at least one m1
or m2 allele but not with subjects diagnosed with lung adenocarcinoma
or small-cel lung cancer.
Discussion: A signicant dierence amoung distribution of CYP1A1(m1)
and CYP1A1(m2) polymorphic varinats between lung cancer subjects
and healthy subjects has been shown. Additionally, the results indicate
that CYP1A1(m1) and CYP1A1(m2) polymorphic variants are associated
with development of squamos cell lung carcinoma, but not of lung adeno-
carcinoma or small-cel lung cancer.
Conclusion: e results of the study demonstrate association between
CYP1A1(m1) and CYP1A1(m2) genetic polymorphisms and signicant
risk of the squamos cell lung carcinoma development.
Disclosure Statement: e authors declare no conict of interest
868
Safety and ecacy outcomes with durvalumab after
sequential chemoradiotherapy (sCRT) in stage III,
unresectable NSCLC (PACIFIC-6)
Helge Bischo1; Marina Chiara Garassino2,3; Julien Mazieres4;
Martin Reck5; Christos Chouaid6; Laura Cove-Smith7; Talal Mansy8;
Maria R. Migliorino9; Angelo Delmonte10; José Garcia Sánchez11;
Luis Enrique Chara Velarde12; Reyes Bernabe13; Luis Paz-Ares14;
Ignacio Diaz Perez15; Nataliya Trunova15; Kayhan Foroutanpour15;
Corinne Faivre-Finn7; Niels Reinmuth16
1Thoraxklinik, Heidelberg, Deutschland
2Fondazione IRCCS Istituto Nazionale dei Tumori, Mailand, Italien
3Department of Hematology/Oncology, The University of Chicago, Chicago, USA
4Institut Universitaire du Cancer de Toulouse, Toulouse, Frankreich
5German Center for Lung Research, Grosshansdorf, Deutschland
6Service de Pneumologie, Centre Hospitalier Intercommunal de Créteil, Créteil,
Frankreich
7The Christie NHS Foundation Trust and Manchester University Hospitals
Foundation Trust, Manchester, Vereinigtes Königreich
8South Tees Hospitals NHS Foundation Trust, Middlesbrough, Vereinigtes
Königreich
9Oncology Unit, ASST-Monza, San Gerardo Hospital, Monza, Italien
10San Camillo-Forlanini Hospital, Rom, Italien
11Medical Oncology Department, Hospital Arnau de Vilanova, Fundación para el
Fomento de la Investigación Sanitaria i Biomédica de la Comunidad Valenciana
(FISABIO), Valencia, Spanien
12Hospital Universitario de Guadalajara, Guadalajara, Spanien
13Hospital Universitario Virgen del Rocio, Sevilla, Spanien
14Universidad Complutense, CiberOnc, CNIO and Hospital Universitario 12 de
Octubre, Madrid, Spanien
15AstraZeneca, Gaithersburg, USA
16Thoracic Oncology, Asklepios Fachkliniken München-Gauting, Gauting,
Deutschland
Background: In the ph 3 PACIFIC trial, durvalumab (durva) aer con-
current CRT (cCRT) signicantly improved survival in pts with Stage
III, unresectable NSCLC. As many pts are ineligible for cCRT, the ph 2
PACIFIC-6 trial aims to assess safety with durva aer sequential CRT
(sCRT).
Methods: Pts with ECOG PS ≤2 and no progression aer Pt-based sCRT
were enrolled to receive durva 1500mg IV q4w ≤24 mths or until progres-
sion, unacceptable toxicity or consent withdrawal. e primary endpoint
was safety/tolerability of durva, dened by the incidence of grade 3/4
possibly related AEs (PRAEs) occurring within 6 mths of treatment (Tx)
initiation. PFS, ORR and OS, were secondary endpoints.
Result: 117 pts were enrolled; 114 (97.4%) had PS 0/1 and 3 (2.6%) had PS
2. Median age was 68.0 years (65.8% were aged ≥65), 62.4% were male and
37.6%/50.4%/11.1% had Stage IIIA/B/C NSCLC. 98.3% had past/present
medical conditions, mostly vascular (59.0%), respiratory (53.8%) and met-
abolic (51.3%) disorders. Median Tx duration was 32.0 weeks (37.6% were
ongoing Tx at data cuto). In all, 94.9% of pts had any AEs and 76.9% had
PRAEs. 18.8% had grade 3/4 AEs and 4.3% had grade 3/4 PRAEs (1.7%
had grade 3/4 PRAE pneumonitis); all pts with grade 3/4 PRAEs had these
events occur within 6 mths (4.3%; 95% CI, 1.4–9.7). 21.4% and 16.2% had
AEs and PRAEs leading to Tx discontinuation, respectively; pneumonitis
was the most common PRAE leading to discontinuation (10.3%). 2 pts
(1.7%) had fatal AEs; 1 was a PRAE (pneumonitis). Ecacy outcomes are
listed in the table.
Ecacy outcomes All patients (N=117) PS 0/1 cohort (N=114)
Median PFS, mths (95% CI) 10.9 (7.3–15.6) 13.1 (7.4–16.7)
12-mth PFS, % (95% CI) 49.6 (39.5–58.9) 50.1 (39.9–59.5)
Median OS, mths (95% CI) 25.0 (25.0–NC) 25.0 (25.0–NC)
12-mth OS, % (95% CI) 84.1 (75.6–89.9) 84.6 (76.0–90.3)
Conrmed ORR, % (95% CI) 17.1 (11.1–25.8) 17.5 (11.4–26.4)
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts160
Conclusion: Durva aer sCRT had a similar safety prole to that observed
with durva aer cCRT in the PACIFIC trial and showed encouraging pre-
liminary ecacy in a frailer and older population.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
908
Durvalumab (D) ± tremelimumab (T) + platinum-etoposide
(EP) in 1L extensive-stage (ES) SCLC: characteristics of
long-term survivors in the CASPIAN study
Jonathan W Goldman1; Marina Chiara Garassino2; Yuanbin Chen3;
Katsuyuki Hotta4; Artem Poltoratskiy5; Maximilian J Hochmair6;
Mustafa Özgüroğlu7; Jun Ho Ji8; Galina Statsenko9; Oleksandr Voitko10;
Nikolay V Conev11; Igor Bondarenko12; Helen Mann13; Mingchao Xie14;
Yashaswi Shrestha15; Priti Chugh14; Tapashi Dalvi15; Luis Paz-Ares16;
Helge Bischo17
1David Geen School of Medicine at UCLA, Los Angeles, USA
2Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italien
3Cancer & Hematology Centers of Western Michigan, Grand Rapids, USA
4Okayama University Hospital, Okayama, Japan
5Petrov Research Institute of Oncology, St. Petersburg, Russische Föderation
6Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Klinik
Floridsdorf, Vienna, Österreich
7Istanbul UniversityCerrahpaşa, Cerrahpaşa School of Medicine, Istanbul,
Türkei
8Samsung Changwon Hospital, Sungkyunkwan University School of Medicine,
Changwon, Republik Korea
9Omsk Regional Cancer Center, Omsk, Russische Föderation
10Kyiv City Clinical Oncological Centre, Kiev, Ukraine
11Clinic of Medical Oncology, UMHAT St Marina, Varna, Bulgarien
12Dnipropetrovsk Medical Academy, Dnipro, Ukraine
13AstraZeneca, Cambridge, Vereinigtes Königreich
14AstraZeneca, Waltham, USA
15AstraZeneca, Gaithersburg, USA
16Hospital Universitario 12 de Octubre, H120-CNIO Lung Cancer Unit,
Universidad Complutense and Ciberonc, Madrid, Spanien
17Thoraxklinik Heidelberg gGmbH , University hospital Heidelberg, Heidelberg,
Deutschland
Background: In the Phase 3 CASPIAN trial, 1L D+EP signicantly
improved OS vs EP and OS benet was sustained aer >3 years median
follow-up (HR 0.71; 95% CI 0.60‒0.86; nominal p=0.0003). Here we assess
clinical and molecular characteristics of pts who experienced long-term
survival in CASPIAN.
Methods: 805 pts with ES-SCLC were randomised 1:1:1 to D+EP, D+T+EP
or EP. In post-hoc analyses, clinical characteristics were assessed in long-
term survivors (LTS; n=94), dened as pts still alive at the 22 Mar 2021
data cuto (DCO; median follow-up 39.4 mo). PD-L1 expression and tis-
sue tumour mutational burden (tTMB) were assessed in the biomarker
evaluable populations (BEPs) according to OS landmark (18 and 36 mo).
Results: ere were 44 (16%), 37 (14%) and 13 (5%) LTS in the D+EP,
D+T+EP and EP arms, respectively. LTS had slightly higher incidence
of some favourable prognostic factors at baseline; incidence of brain/
liver mets was lower among LTS vs ITT, although they still occurred
in some LTS. More LTS received ≥4 cycles EP than ITT, with a higher
median overall treatment exposure in the IO+EP arms. 46 (27 D+EP; 19
D+T+EP) LTS were ongoing D treatment at this DCO. ORR and 24-mo
PFS rates were higher for LTS vs ITT in the IO+EP arms. Rates of serious
AEs (SAEs) were similar in LTS and ITT. In the D+T+EP arm only, inci-
dence of PD-L1 expression on ≥1% of tumour cells (TC) or immune cells
(IC) (but not tTMB >10 mut/Mb) was enriched in pts with OS ≥18 mo
vs OS <18 mo; enrichment was maintained with OS ≥36 mo (data will be
presented).
Discussion & Conclusion: ere were >3 times as many LTS in the D+EP
arm vs the EP arm. LTS were more likely to have favourable prognos-
tic characteristics than ITT, although some LTS had brain/liver mets at
baseline. Notably, most LTS completed EP induction and, in both the
IO+EP arms, had substantially greater overall treatment exposure, as well
as achieving higher ORR and longer PFS, vs ITT. ere was no evidence
of cumulative toxicity based on SAEs.
Indication of source: Reinmuth, N. et al, ELCC 2022
Funding: AstraZeneca
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
912
Clinical and Molecular Characteristics of small-scale ROS1
aberrations in non-small cell lung cancer patients
Moritz Glaser1; Cornelia von Levetzow1; Sebastian Michels1; Lucia
Nogova1; Marianna Katzenmeier1; Claudia Wömpner1; Jaqueline
Schmitz1; Elisabeth Bitter1; Inken Terjung1; Elke Passmann1; Diana
Schauer1; Anna Eisert1; Rieke Fischer1; Richard Riedel1; Jan-Phillip Weber1;
Sabine Hahne1; Sabine Merkelbach-Bruse2; Reinhard Büttner2;
JürgenWolf1; Matthias Scheer1
1University Hospital of Cologne, Department I of Internal Medicine, Köln,
Deutschland
2University of Cologne, Cologne Institute of Pathology, Köln, Deutschland
Background: Fusions in the ROS1 proto-oncogene are among the best
treatable genetic aberrations in Non-small cell lung cancer (NSCLC).
Besides the occurrence of solvent-front mutations (SFM) in acquired
resistance to targeted therapy, little is known about ROS1 aberrations
other than fusions. We analyzed molecular and clinical characteristics of
ROS1 mutations in NSCLC patients without activating ROS1 fusions or
SFMs.
Methods: Next-generation sequencing (NGS) was performed on tissue
samples from NSCLC patients within the National Network Genomic
Medicine (nNGM). Patients with activating ROS1 fusions detected by
uorescence in-situ hybridization (FISH) were excluded. We analyzed
the mutations’ frequencies and characteristics as well as co-occurring
mutations.
Result: Of 8072 patients analyzed by NGS between 2018 and 2021, 118
(1.5%) patients harbored ROS1 mutations. Most patients were male
(76.3%) and had adenocarcinoma histology (57.6%). e median age at
diagnosis amounted to 68 years. Nearly all of the patients (96.5%) had a
smoking history, amassing 40 pack-years on average. e most frequent
ROS1 mutations were transversions (53.6%), without dening a genomic
hotspot region. Besides TP53 mutations (61.0%), KRAS (25.4%), EGFR
(7.6%), PIK3CA and FGFR1-4 mutations (5.9% each) co-occurred most
frequently. In 12 (10.2%) patients, ROS1 mutation was the only detected
aberration.
Discussion: Our cohort opposites the clinical characteristics of patients
with ROS1 fusion regarding sex, smoking history, age, and histology.
Conclusion: Further research is warranted to characterize their biological
impact and their potential to act as a drug target.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 161
920
Five-year survival outcomes with nivolumab (NIVO) +
ipilimumab (IPI) vs chemotherapy (chemo) as rst-line
(1L) treatment for metastatic non-small cell lung cancer
(mNSCLC): Results from CheckMate 227
Martin Reck1; Julie R. Brahmer2; Jong-Seok Lee3; Tudor-Eliade Ciuleanu4;
Reyes Bernabe Caro5; Makoto Nishio6; Laszlo Urban7;
Clarisse Audigier-Valette8; Lorena Lupinacci9; Randeep Sangha10;
Luis Paz-Ares11; Hossein Borghaei12; Kenneth John O’byrne13;
Ravi G. Gupta14; Judith Bushong14; LI LI14; Steven I. Blum14; Laura Eccles14;
Suresh S. Ramalingam15
1Airway Research Center North, German Center for Lung Research, LungClinic,
Grosshansdorf, Deutschland
2Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins
Kimmel Cancer Center, Baltimore, MD, USA
3Seoul National University Bundang Hospital, Seongnam, Republik Korea
4Institutul Oncologic Prof Dr Ion Chiricuta and University of Medicine and
Pharmacy Iulia Hatieganu, Cluj-Napoca, Rumänien
5Hospital Universitario Virgen Del Rocio, Instituto de Biomedicina de Seville,
Seville, Spanien
6Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo,
Japan
7Mátrai Gyógyintézet, Matrahaza, Ungarn
8Orientation Oncologique (pole14), Hôpital Sainte-Musse, Toulon, Frankreich
9Hospital Italiano de Buenos Aires, Buenos Aires, Argentinien
10Cross Cancer Institute, Edmonton, Kanada
11Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid,
Madrid, Spanien
12Fox Chase Cancer Center, Philadelphia, PA, USA
13Princess Alexandra Hospital, Translational Research Institute and Queensland
University of Technology, Brisbane, Australien
14Bristol Myers Squibb, Princeton, NJ, USA
15Winship Cancer Institute, Emory University, Atlanta, GA, USA
Background: In CheckMate 227 part 1 (NCT02477826), 1L NIVO + IPI
demonstrated long-term, durable survival benet vs chemo in patients
(pts) with mNSCLC regardless of PD-L1 expression level. Here we present
the longest reported follow-up (5 y) of a phase 3 trial of 1L combination
immunotherapy in mNSCLC.
Methods: Adults with tx-naïve stage IV/recurrent NSCLC, no known
EGFR/ALK alterations, and ECOG performance status ≤ 1 were enrolled.
Pts with tumor PD-L1 ≥ 1% were randomized 1:1:1 to NIVO (3 mg/kg
Q2W) + IPI (1 mg/kg Q6W), NIVO (240 mg Q2W), or chemo. Pts with
tumor PD-L1 < 1% were randomized 1:1:1 to NIVO + IPI, NIVO (360
mg Q3W) + chemo, or chemo. Pts were treated until progression, toxicity
or ≤ 2 y for NIVO±IPI. Assessments included overall survival (OS), pro-
gression-free survival (PFS), objective response rate (ORR), duration of
response (DOR), and tx-free interval (measured in pts who are o study tx
for any reason including treatment completion and dened as time from
last dose to start of subsequent systemic tx or death).
Results: Minimum follow-up was 61.3 mo (database lock: Feb 15, 2022).
In pts with tumor PD-L1 ≥ 1% (N = 1189), long-term OS benet contin-
ued with NIVO + IPI vs chemo (HR 0.77; 95% CI 0.66–0.91); 5-y OS rates
were 24% (NIVO + IPI) and 14% (chemo). OS benet also continued in
pts with tumor PD-L1 < 1% (N = 550) for NIVO + IPI vs chemo (HR 0.65;
0.52–0.81); 5-y OS rates were 19% (NIVO + IPI) and 7% (chemo). Clinical
benet with NIVO + IPI vs chemo was observed in the overall population
(5-y DOR rates, PD-L1 ≥ 1%: 28% vs 3%; PD-L1 < 1%: 21% vs not appli-
cable, NA) and in pts alive at 5 y (5-y DOR rates, PD-L1 ≥ 1%: 54% vs
17%; PD-L1 < 1%: 41% vs NA). OS, PFS, ORR and DOR with NIVO and
NIVO + chemo will be presented. Of pts alive at 5 y in the NIVO + IPI
arm, 66% (PD-L1 ≥ 1%) and 64% (PD-L1 < 1%) were tx-free ≥ 3 y post-tx
discontinuation. No new safety signals were noted.
Conclusions: With a 5-y minimum follow-up, NIVO + IPI long-term,
durable clinical benet vs chemo is maintained for tx-naïve mNSCLC,
regardless of PD-L1 expression. NIVO + IPI increased 5-y survivorship;
most pts were tx-free for ≥ 3 y post-tx discontinuation.
©2022 American Society of Clinical Oncology, Inc. Reused with
permission. is abstract was accepted and previously presented at the
2022 ASCO Annual Meeting. All rights reserved.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
942
First-line (1L) nivolumab (NIVO) + ipilimumab (IPI) + 2
cycles of chemotherapy (chemo) vs chemo alone (4 cycles)
in patients (pts) with metastatic non-small cell lung cancer
(mNSCLC): 3-year update from CheckMate 9LA
Niels Reinmuth1; Luis Paz-Ares2; Tudor-Eliade Ciuleanu3;
Manuel Cobo-Dols4; Jaafar Bennouna5; Ying Cheng6; Hideaki Mizutani7;
Alejo Lingua8; Felipe Reyes9; Juliana Menezes10; Jacek Jassem11;
Svetlana Protsenko12; Kynan Feeney13; Emmanuel de la Mora Jimenez14;
Shun Lu15; Thomas John16; David Paul Carbone17; Xiaoqing Zhang18;
Nan Hu18; Martin Reck19
1Asklepios Lung Clinic Munich-Gauting, Gauting, Deutschland
2Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid,
Madrid, Spanien
3Institutul Oncologic Prof Dr Ion Chiricuta and University of Medicine and
Pharmacy Iulia Hatieganu, Cluj-Napoca, Rumänien
4Unidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales
Universitarios Regional y Virgen de la Victoria, IBIMA, Málaga, Spanien
5University Hospital of Nantes and INSERM, CRCINA, Nantes, Frankreich
6Jilin Cancer Hospital, Changchun, China, VR
7Saitama Cancer Center, Saitama, Japan
8Instituto Medico Rio Cuarto SA, Córdoba, Argentinien
9Fundacion Arturo Lopez Perez, Santiago, Chile
10Hospital Nossa Senhora da Conceição, Porto Alegre, Brasilien
11Medical University of Gdańsk, Gdańsk, Polen
12N.N. Petrov National Medical Research Center of Oncology, St. Petersburg,
Russische Föderation
13St John of God Hospital Murdoch, Perth, Australien
14Instituto Jalisciense De Cancerología, Guadalajara, Mexiko
15Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai JiaoTong
University, Shanghai, China, VR
16Austin Hospital, Heidelberg, Australien
17The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
18Bristol Myers Squibb, Princeton, NJ, USA
19Airway Research Center North, German Center for Lung Research, LungClinic,
Grosshansdorf, Deutschland
Background: In CheckMate 9LA (NCT03215706), 1L NIVO + IPI com-
bined with 2 cycles of chemo was shown to provide survival benet vs
chemo alone in pts with mNSCLC. Here, we report updated ecacy and
safety with a 3-y minimum follow-up (f/u), as well as exploratory bio-
marker analyses.
Methods: Adults with stage IV/recurrent NSCLC, no known sensitizing
EGFR/ALK alterations, and ECOG performance status ≤ 1 were ran-
domized 1:1 to NIVO 360 mg Q3W + IPI 1 mg/kg Q6W + 2 cycles of
chemo (n = 361) or 4 cycles of chemo alone (n = 358). Pts were stratied
by tumor PD-L1 expression, sex, and histology. Pts with non-squamous
(NSQ) NSCLC in the chemo arm could receive pemetrexed maintenance.
Assessments included overall survival (OS), progression-free survival
(PFS), and objective response rate (ORR). For pts with NSQ NSCLC and
tissue evaluable for mutational analysis (n = 313), mutant (mut) or wild
type (wt) KRAS and STK11 genes were identied via the FoundationOne
CDxTM assay. Exploratory assessments included OS and PFS by mutation
status and safety.
Results: At a minimum f/u of 36.1 mo (database lock: Feb 15, 2022), pts
continued to derive long-term, durable OS benet with NIVO + IPI +
chemo vs chemo (HR 0.74 [95% CI 0.62–0.87]); 3-y OS rates were 27%
vs 19%. Clinical benet with NIVO + IPI + chemo vs chemo was also
observed across most subgroups, including by PD-L1 <1% (HR 0.67
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts162
[0.51–0.88]), PD-L1 ≥1% (HR 0.74 [0.60–0.93]) or histology. In an
exploratory analysis in pts evaluable for mutations, median OS appeared
improved with NIVO + IPI + chemo vs chemo (16.3 vs 13.1 mo). e
trend of prolonged median OS with NIVO + IPI + chemo vs chemo was
also seen in pts with/without KRAS mutation (mut: 19.2 vs 13.5 mo; wt:
15.6 vs 12.7 mo) or STK11 mutation (mut: 13.8 vs 10.7 mo; wt: 17.8 vs 13.9
mo), respectively. Additional ecacy outcomes will be presented. No new
safety signals were found with extended f/u.
Conclusions: With a 3-y minimum f/u, 1L NIVO + IPI + chemo demon-
strated long-term, durable ecacy benet vs chemo in pts with mNSCLC.
Survival benet of NIVO + IPI + chemo vs chemo was seen regardless of
KRAS and STK11 mutation status.
©2022 American Society of Clinical Oncology, Inc. Reused with per-
mission. is abstract was accepted and previously presented at the 2022
ASCO Annual Meeting. All rights reserved.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
964
Evaluation of quality of life and survival time of lung cancer
patients treated in a certied German lung cancer center; a
real-world data study
Shiao Li Oei1; Anja Thronicke1; Hannah Wüstefeld2; Burkhard Matthes1,2;
Christian Grah2; Friedemann Schad1,3
1Forschungsinstitut am Gemeinschaftskrankenhaus Havelhöhe , Netzwerk
Onkologie, Berlin, Deutschland
2Gemeinschaftskrankenhaus Havelhöhe , Pneumologie , Onkologisches
Zentrum, Berlin, Deutschland
3Gemeinschaftskrankenhaus Havelhöhe , Interdisziplinäre Onkologie und
Palliativmedizin, Berlin, Deutschland
Background: Lung cancer (LC) is associated with high mortality and poor
quality of life (QoL) but due to advances in prognosis and treatments sur-
vival time is increasingly improving. e aim of this study was to analyze
associations between self-reported QoL and survival time in guide-line
treated LC patients in a real-world setting.
Methods: e real-world-data (RWD) study was conducted using
data from an oncological registry accredited by the German Cancer
Society. e study received positive ethics approval and was registered
(DRKS00013335 on 27/11/2017). Self-reported QoL of LC patients was
assessed by evaluation of the European Organization of Research and
Treatment Health-Related Quality of Life Core Questionnaire scale
(EORTC QLQ-C30). Association factors between QoL and survival time
were analyzed by adjusted multivariate linear regression analyses, using
the soware R.
Result: A total of 224 primary LC patients (all stages, median age 69 years)
answered QoL questionnaires at rst LC diagnosis and their dates of death
were documented. e median survival time of the entire study cohort
was 9.8 months (ICR: 4.7-17.5 months). Patients with early tumor stages,
if they could be surgically treated or undergo irradiation, or females sur-
vived signicantly longer. Among QoL parameters, a signicant associa-
tion was found between better self-reported nausea/vomiting scales and
prolonged survival (p=0.004), and similarly for appetite (p=0.03).
Discussion: QoL data and their impact on survival in LC patients are
poorly understood. Our results suggest that there may be a relevant asso-
ciation between certain QoL parameters self-reported at LC diagnosis and
survival time.
Conclusion: Our ndings suggest that nausea/vomiting and appetite
appear to be prognostic survival factors for LC patients.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
989
Cobolimab With Dostarlimab and Docetaxel in Patients (pts)
With Advanced Non-small Cell Lung Cancer (NSCLC): COSTAR
Lung
Hye Ryun Kim1; Cesare Gridelli2; Dinesh Kapur3; Amanda Tufman4;
Enriqueta Felip5; Vamsidhar Velcheti6; Yu Jung Kim7; Thorsten Götze8;
Pilar Garrido Lopez9; Romain Corre10; Konstantin Penkov11; Rana Anjum12;
Brian DI Pace12; Wenlei Liu12; Theo Borgovan12; Danielle Ledger12;
Jennifer Carver12; Angela Waszak12; Arindam Dhar12; Silvia Novello13
1Yonsei University College of Medicine
2S.G. Moscati Hospital
3Eastern Connecticut Hematology and Oncology
4Thoracic Oncology Centre Munich
5Vall dHebron University Hospital
6NYU Langone Health
7Seoul National University College of Medicine
8Institute of Clinical Cancer Research, Krankenhaus Nordwest, UCT University
Cancer Center
9Hospital Universitario Ramón y Cajal
10Centre Hospitalier Universitaire de Rennes
11Private Medical Institution Euromedservice
12GlaxoSmithKline
13University of Turin, San Luigi Hospital
Background: e Ph1 AMBER study (NCT02817633) showed that
cobolimab (GSK4069889, TIM-3 inhibitor) + dostarlimab (PD-1 inhib-
itor) had an acceptable safety prole in heavily pretreated, PD-1/PD-L1
relapsed/refractory (RR), advanced or metastatic NSCLC.
COSTAR Lung (NCT04655976) compares ecacy and safety of cobo-
limab + dostarlimab and SOC chemotherapy (CT, docetaxel; Arm A) to
dostarlimab + docetaxel (Arm B) to docetaxel (Arm C) in PD-1/PD-L1
RR NSCLC.
Methods: is is an ongoing global, multicenter, parallel-group treatment,
randomized, Ph2, open-label, 3-arm study, with potential Ph3 expansion.
Pts are ≥18 years, with advanced/metastatic NSCLC who received ≤2 prior
lines of therapy including anti-PD-1/PD-L1 therapy plus platinum-based
CT only. Other inclusion criteria include documented disease progression
(PD) on prior therapy, no sensitizing EGFR, ALK or ROS-1 mutations,
and ECOG PS 0–1.
Pts randomized 2:2:1 to Arms A, B, or C will receive cobolimab (300mg
IV), dostarlimab (500 mg IV), and/or docetaxel (75 mg/m2 IV) Q3W.
Cobolimab + dostarlimab will continue until PD, unacceptable toxicity,
withdrawal, investigator decision, or death. Docetaxel will continue for ≥4
cycles or until unacceptable toxicity or PD.
Primary endpoint: OS in Arms A or B vs C. Secondary endpoints: OS
in Arm A vs B and investigator-assessed conrmed objective response
rate (ORR); progression-free survival (PFS) and duration of response
(RECIST v1.1); quality of life assessments; safety; and tolerability.
Exploratory endpoints: investigator-assessed conrmed ORR and PFS
(iRECIST), pharmacokinetics, biomarkers of response, and pt-reported
ecacy/tolerability.
Result:
Discussion:
Conclusion: Approximately 250 pts will be randomized to Ph2 portion
with interim analysis planned aer ≥18 weeks follow-up; with an addi-
tional 500 pts (Arms A–B [n=200 each] and Arm C [n=100]) in Ph3
portion.
Funding: GSK (213410, NCT04655976). Previously presented at IASLC-
WCLC 2021 and submitted to DKK 2022 on behalf of original authors
with their permission.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 163
1007
Nintedanib in combination with nivolumab in pretreated
patients with advanced adenocarcinoma of the lung
(AIO-TRK-0117 Phase Ib/II trial)
Martin Sebastian1; Parvis Sadjadian2; Cornelius Waller3; Kato Kambartel4;
Christian Grohé5; Achim Rittmeyer6; Andrea Sendler7; Niels Reinmuth8;
Ralph Keller9; Hanna von Suchdoletz9; Martin Mänz9; Martin Reck10
1Universitätsklinikum Frankfurt Goethe Universität, Med. Klinik 2, Hämatologie/
Medizinische Onkologie, Frankfurt, Deutschland
2Universitätsklinik für Hämatologie, Onkologie, Hämostaseologie und
Palliativmedizin, Johannes Wesling Klinikum Minden, Universitätsklinikum der
Ruhr-Universität Bochum, Minden, Deutschland
3Universitätsklinikum Freiburg, Klinik für Innere Medizin I, Schwerpunkt
Hämatologie, Onkologie und Stammzelltransplantation, Freiburg, Deutschland
4Stiftung Bethanien Krankenhaus Moers, Klinik für Lungen- und
Bronchialheilkunde, Moers, Deutschland
5Evangelische Lungenklinik Berlin, Klinik für Pneumologie, Berlin, Deutschland
6Lungenfachklinik Immenhausen, Zentrum für Pneumologie, Immenhausen,
Deutschland
7Klinikum Hanau, Medizinische Klinik III, Hanau, Deutschland
8Asklepios Fachkliniken München-Gauting, Thorakale Onkologie, Gauting,
Deutschland
9AIO-Studien-gGmbH, Berlin, Deutschland
10LungenClinic Grosshansdorf, Thoraxonkologie, Deutsches Zentrum für
Lungenforschung. , Großhansdorf, Deutschland
Background: Nivolumab und Nintedanib sind etablierte Zweitlinien
therapien des nicht-plattenepithelialen NSCLC. NintNivo untersucht
das Potential einer Kombination der beidenerapieprinzipien in fort-
geschrittenen erapielinien des nicht-kleinzelligen Adenokarzinoms
derLunge
Methods: In der multizentrischen, oenen, einarmigen Phase Ib Studie
wurden Patient*innen (Pat) mit lokal fortgeschrittenem/metastasiertem
Adeno-NSCLC nach Versagen einer platinbasierten Chemotherapie
+/- Checkpointinhibitor (CPI) mit der Kombination Nintedanib und
Nivolumab behandelt. Nach einer klassischen Dosisndung im 3 +3
Design erhielten die Pat 200mg Nintedanib BID und 240mg Nivolumab
Q2W. Primäre Endpunkte waren Sicherheit, Verträglichkeit sowie pro-
gressionsfreies Überleben (PFS) nach 6 und 12 Monaten. Sekundäre
Endpunkte waren unter anderem die objektive Ansprechrate (ORR), PFS,
Gesamtüberleben (OS) und die Rate unerwünschter Ereignisse (AE).
Result: Im Phase 1b Teil zeigte sich keine dosislimitierende Toxizität sodass
53 Pat mit einem medianen Alter von 64 Jahren randomisiert wurden.
Die Mehrzahl erhielt in der Erstlinie eine platinhaltige Chemotherapie +/-
CPI, 15,1% erhielten zwei erapielinien vor Randomisierung. Die vorläu-
gne Ergebnisse zeigen eine ORR von 11,3% und eine stabile Erkrankung
bei 30,2% als bestes Ansprechen. Die PFS-Rate nach 6 und 12 Monaten
und das Gesamt-PFS waren 24.5% (95% CI, 14.0% bis 36.6%),10.5% (95%
CI 4.0% bis 20.8%) und 2.5 Monate. Die 1-Jahres OS-Rate war 53%, das
mediane OS 12,5 Monate. Behandlungsbedingte AEs fanden sich bei
86,6% der Pat, behandlungsbedingte AEs Grad 3 und höher bei 38,8%.
Conclusion: Unsere vorläugen Ergebnisse zeigen die Machbarkeit und
klinische Aktivität der Kombination von Nintedanib mit Nivolumab bei
Pat mit fortgeschrittenem/metastasierten Adenokarzinom der Lunge nach
Versagen einer Erstlinientherapie. Weitere Analysen und translationale
Untersuchungen untersuchen welche Pat von dieser erapie protieren.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
1047
Pembrolizumab Maintenance Following First-Line Platinum
Based Chemotherapy in Patients with Metastatic Squamous
Non-Small Cell Lung Cancer (sqNSCLC) – AIO-TRK-0115/
PRIMUS
Parvis Sadjadian1; Jens Kollmeier2; Jens Kern3; Petra Hoknecht4;
Martin Sebastian5; Amanda Tufman6; M Maenz7; Martin Reck8
1Johannes Wesling Klinikum Minden, Universitätsklinik für Hämatologie,
Onkologie, Gerinnungsstörungen und Palliativmedizin, Minden,
2Helios Klinikum Emil von Behring Berlin
3Klinikum Würzburg Mitte Missioklinik
4Franziskus Hospital Harderberg, Georgsmarienhütte
5Universitätsklinikum Frankfurt
6LMU Universitätsklinik München
7AIO Studien gGmbH Berlin
8LungenClinic Grosshansdorf
Purpose: To improve outcomes for patients with advanced squamous
NSCLC, the phase II multi-center, double-blind PRIMUS trial was con-
ducted to explore the potential of pembrolizumab maintenance treatment
aer platinum-based induction chemotherapy.
Methods: Stage IV squamous NSCLC patients with least stable disease
aer at least 2 cycles of rst-line platinum-based chemotherapy were
randomized 1:1 to Q3W pembrolizumab maintenance treatment or
placebo, irrespective of tumor PD-L1 expression, for a maximum of 2
years. Primary endpoint was progression-free survival (PFS), secondary
endpoints included objective response rate (ORR), overall survival (OS),
PD-L1 expression in tumor samples, safety and tolerability, and quality of
life by FACT-L and LCSS questionnaires.
Results: Planned patient enrollment of 65 per arm was not met due
to changes of clinical treatment standards for rst-line treatment.
Pembrolizumab maintenance was administered to 16 patients, 18 patients
received placebo. Survival results favor Pembrolizumab maintenance
over placebo: Median PFS was 9.5 mo [95% CI 1.5-23.5] vs 4.8 mo [95%
CI 1.8-10.5]. PFS rate at 6, 12 and 18 months was 50.3% [95% CI 23.1-
72.4%], 35.9% [95% CI 13.1-59.6%] and 35.9% [95% CI 13.1-59.6%] vs
36.1% [95% CI 15.0-57.9%], 18.1% [95% CI 4.5-39.0%] and 9.0% [95% CI
0.7-30.9%]. Median OS was 24.0 mo [95% CI 9.5-30.9] vs 10.9 mo [95%
CI 4.8-39.2]. OS rates at 6 and 12 months were 86.7% [95% CI 56.4-96.5%]
and 79.4% [95% CI 48.8-92.9%] vs 69.3% [95% CI 41.1- 85.9] and 44.1%
[95% CI 20.0-65.9%]. AEs ≥ grade 3 potentially related to Pembrolizumab
according to investigator assessment occurred in 4 patients: grade 3
hyperthyreosis, myocarditis, nephritis and acute renal failure, and grade 4
bronchopulmonary hemorrhage.
Conclusion: Our results indicate a notable benet of the pembrolizumab
maintenance strategy compared to placebo in terms of survival. is is a
remarkable nding given that the number of treated patients was consid-
erably lower than planned. Further exploration is warranted.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts164
Lymphoma and Plasma Cell Disorders
Best-of-Abstract-Vortrag
891
Polatuzumab vedotin plus rituximab, cyclophosphamide,
doxorubicin, and prednisone (pola-r-chp) versus rituximab,
cyclophosphamide, doxorubicin, vincristine and prednisone
(r-chop) therapy in patients with previously untreated diuse
large b-cell lymphoma (dlbcl): results from the phase iii
polarix study
sascha Dietrich1; Hervé Tilly2; Franck Morschhauser3; Laurie H. Sehn4;
Jonathan W. Friedberg5; Marek Trněný6; Je Sharman7; Charles Herbaux8;
John M. Burke9; Matthew Matasar10; Shinya Rai11; Koji Izutsu12; Neha
Mehta-Shah13; Lucie Oberic14; Adrien Chauchet15; Wojciech Jurczak16;
Yu Qin Song17; Richard Greil18; Larysa Mykhalska19;
Juan Miguel Bergua Burgués20; Matthew C. Cheung21; Antonio Pinto22;
Ho-Jin Shin23; Greg Hapgood24; Eduardo Munhoz25; Gilles Salles26
1Klinik für Hämatologie, Onkologie, Rheumatologie, Universitätskilinikum
Heideberg, Heidelberg, Deutschland
2Centre Henri Becquerel and University of Rouen, Rouen, Frankreich
3Univ. Lille, CHU Lille, Group de Recherche sur les formes Injectables et les
Technologies Associées, Lille, Frankreich
4BC Cancer Centre for Lymphoid Cancer and the University of British Columbia,
Vancouver, Kanada
5UR MedicineWilmot Cancer Center, Rochester, USA
6First Faculty of Medicine, Charles University, General Hospital, Prag, Tschechien
7Willamette Valley Cancer Institute/US Oncology, Eugene, USA
8CHU de Montpellier, Montpellier, Frankreich
9Rocky Mountain Cancer Centers/US Oncology, Aurora, USA
10Memorial Sloan Kettering Cancer Center, New York City/Montvale, USA
11Kindai University, Faculty of Medicine, Osaka-Sayama City, Japan
12National Cancer Center Hospital, Tokyo, Japan
13Washington University in St. Louis, St. Louis, USA, MO
14Institut Universitaire du Cancer, Toulouse-Oncopole, Toulouse, Frankreich
15Department of Hematology, CHRU Besançon, Besançon, Frankreich
16Maria SklodowskaCurie National Research Institute of Oncology, Kraków,
Polen
17Peking University Cancer Hospital, Beijing
18Paracelsus Medical University, Salzburg Cancer Research Institute-CCCIT and
Cancer Cluster Salzburg, Salzburg, Österreich
19Clinical Hospital Feofaniya, Kyiv, Ukraine
20Hospital San Pedro de Alcántara, Cáceres, Spanien
21Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of
Toronto, Toronto, Kanada
22Hematology-Oncology & Stem Cell Transplantation Unit, Istituto Nazionale
Tumori, FondazioneG. Pascale’, IRCCS, Naples, Italien
23Medical Research Institute, Pusan National University Hospital, Pusan National
University School of Medicine, Busan, Südkorea
24Princess Alexandra Hospital, Brisbane, Australien
25Hospital Erasto Gaertner, Curitiba, Brasilien
26Memorial Sloan Kettering Cancer Center, New York City, USA
Background: R-CHOP is standard of care for newly diagnosed DLBCL
patients (pts), yet 40% remain uncured. Polatuzumab vedotin, a CD79b-
targeting antibody-drug conjugate, has shown promising activity in a
Phase Ib/II study. We report POLARIX (NCT03274492), a double-blind,
placebo-controlled, international Phase III study comparing Pola-R-CHP
vs R-CHOP in treatment-naïve DLBCL pts with an IPI score of 2–5.
Methods: Pts were randomised (1:1) to 6 cycles of Pola-R-CHP or R-CHOP.
On day 1 of cycles 1–6, pts received polatuzumab vedotin 1.8mg/kg or
vincristine 1.4mg/m² + rituximab 375mg/m2, cyclophosphamide 750mg/
m², and doxorubicin 50mg/m². Pts also received oral prednisone 100mg
on days 1–5 and two further cycles of rituximab. Investigator-assessed PFS
was the primary endpoint.
Result: Overall 879 pts (median age 65 [range 19–80] years) were ran-
domised (Pola-R-CHP: n=440; R-CHOP: n=439). At primary data cut-o
(28 June 2021), median follow-up was 28.2 months. PFS was superior
(HR 0.73; 95% CI: 0.57–0.95; P=0.02) and 2-year PFS rate was improved
(76.7% [95% CI: 72.7–80.8] vs 70.2% [95% CI: 65.8–74.6]) with Pola-
R-CHP vs R-CHOP. EFS favoured Pola-R-CHP vs R-CHOP (HR 0.75
95% CI: 0.58–0.96; P=0.02). While end-of-treatment PET-CT CR
rate was not signicantly dierent with Pola-R-CHP (78.0%) vs
R-CHOP (74.0%), DFS suggested more durable responses (HR 0.70
95% CI: 0.50–0.98). OS was comparable between treatment arms. Similar
safety proles were seen between treatment groups. For Pola-R-CHP vs
R-CHOP, rates of grade 3–4 adverse events (AEs) were 57.7% vs 57.5%,
serious AEs were 34.0% vs 30.6%, grade 5 AEs were 3.0% vs 2.3%, and
AEs leading to dose reduction were 9.2% vs 13.0%, respectively. Rates of
peripheral neuropathy were similar for Pola-R-CHP vs R-CHOP. At data
cut-o, fewer pts treated with Pola-R-CHP (23%) vs R-CHOP (30%) had
received ≥1 subsequent anti-lymphoma therapy.
Conclusion: As rst-line treatment of DLBCL, Pola-R-CHP demon-
strated a 27% reduction in relative risk of disease progression, relapse, or
death, and a similar safety prole, vs R-CHOP.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
967
Phase 3 TRANSFORM study of lisocabtagene maraleucel
(liso-cel), a CD19-directed chimeric antigen receptor
T cell therapy (Tx), versus standard of care (SOC) of
salvage chemotherapy followed by autologous stem cell
transplantation (ASCT) as second-line (2L) Tx in patients (pt)
with relapsed or refractory (R/R) large B-cell lymphoma (LBCL)
Bertram Glaß1; Manali Kamdar2; Scott Solomon3; Jon Arnason4;
Patrick B Johnston5; Sami Ibrahimi6; Stephan Mielke7; Pim Mutsaers8;
Francisco Hernandez-Ilizaliturri9; Koji Izutsu10; Franck Morschhauser11;
Matthew Lunning12; David Maloney13; Alessandro Crotta14;
Sandrine Montheard14; Alessandro Previtali14; Lara Stepan15;
Ken Ogasawara15; Jeremy Abramson16
1Helios Klinikum Berlin-Buch, Berlin, Deutschland
2University of Colorado Cancer Center, Colorado, USA
3Northside Hospital Cancer Institute, USA
4Beth Israel Deaconess Medical Center, Boston, USA
5Mayo Clinic, Rochester, USA
6University of Oklahoma Stephenson Cancer Center, Oklahoma, USA
7Center of Allogeneic Stem Cell Transplantation and Cellular Therapy (CAST),
Karolinska Institutet and University Hospital, Solna, Schweden
8Erasmus University Medical Center, Rotterdam, Niederlande
9Roswell Park Comprehensive Cancer Center, New York, USA
10National Cancer Center Hospital, Singapur, Japan
11Université de Lille, Centre Hospitalier Universitaire de Lille. ULR 7365, GRITA
Groupe de Recherche sur les formes Injectables et les Technologies Associées,
Lille, Frankreich
12University of Nebraska Medical Center, Nebraska, USA
13Fred Hutchinson Cancer Research Center, Seattle, USA
14Celgene, a Bristol-Myers Squibb Company, Zürich, Schweiz
15Bristol-Myers Squibb, Seattle, USA
16Massachusetts General Hospital Cancer Center, Massachusetts, USA
Background: We present a prespecied interim analysis comparing the
investigational CD19-directed CAR T cell product, liso-cel (Arm B), with
SOC (Arm A) as 2L Tx in pts with R/R LBCL in the randomized phase 3
TRANSFORM study (NCT03575351; Kamdar M, et al. in press).
Methods: Pts with LBCL primary refractory to or relapsed ≤12 mo aer
rst-line Tx received liso-cel or SOC (3 cycles of R-DHAP, R-ICE, or
R-GDP, then BEAM+ASCT in responders). Pts were aged 18–75 years
and intended for transplant, with ECOG PS ≤1 and adequate organ
function; secondary CNS lymphoma was allowed. Bridging Tx with an
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 165
SOC regimen was allowed for disease control during liso-cel manufactur-
ing. Primary endpoint was EFS, with response assessed by Independent
Review Committee per Lugano 2014 criteria. Key secondary endpoints
included CR rate, PFS, and OS.
Result: Baseline characteristics were balanced between the 92 pts ran-
domized to each arm. In Arm B, 90 pts received liso-cel infusion; 58 pts
(63%) received bridging Tx. Median follow-up was 6.2 mo (range, 0.9–
20.0). Median EFS was signicantly longer for liso-cel versus SOC (10.1
mo vs 2.3 mo; HR, 0.349; 95% CI, 0.229–0.530; P<0.0001). CR rate and
PFS showed statistically signicant improvements for Arm B. In Arm B,
any-grade cytokine release syndrome (CRS) was reported in 49% of pts;
only 1 pt had grade 3 CRS and 0 had grade 4/5. Any-grade neurological
events were reported in 12% of pts and were primarily low grade (grade
3, 4%; grade 4/5, 0%). In Arm B, 24% of pts received tocilizumab, 17%
received corticosteroids, and none received vasopressors. e most com-
mon treatment-emergent AEs in both arms were cytopenias.
Discussion: In TRANSFORM, liso-cel demonstrated statistically signi-
cant and clinically meaningful improvement in EFS compared with SOC
as 2L Tx. No new liso-cel safety concerns were identied.
Conclusion: Liso-cel improved outcomes versus SOC and exhibited a
favorable safety prole, providing support for liso-cel as a standard 2L Tx
in LBCL.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
Poster
150
Pomalidomide (POM), bortezomib (BORT), and
dexamethasone (DEX) after 1 prior line of therapy in relapsed
or refractory multiple myeloma (RRMM): a safety subanalysis
of the phase 3 OPTIMISMM trial
Katja Weisel1; Meletios Dimopoulos2; Albert Oriol3; Meral Beksac4;
Frederick Schjesvold5; Anna Marina Liberati6; Jindriska Lindsay7;
Darrell White8; Jésus San-Miguel9; Philippe Moreau10;
Larry D. Anderson Jr11; Alessandra Lorocca12; Pawel Robak13; Prisca
Vogel14; Ruiyun Jiang15; Lara Grote15; Teresa Peluso14; Paul Richardson16
1University Medical Center Hamburg-Eppendorf, Hamburg, Deutschland
2National and Kapodistrian University of Athens, Athens, Griechenland
3Institut Català dOncologia-Hospital Germans Trias i Pujol, Josep Carreras
Leukaemia Research Institute, Badalona, Spanien
4Ankara University, Ankara, Türkei
5Oslo Myeloma Center, Oslo University Hospital and KG Jebsen Center for B-cell
malignancies, University of Oslo, Oslo, Norwegen
6University of Perugia, Perugia, Italien
7East Kent Hospitals University NHS Foundation Trust, Kent and Canterbury
Hospital, Canterbury, Vereinigtes Königreich
8Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax,
Kanada
9Clinica Universidad de Navarra, Pamplona, Spanien
10University Hospital Hôtel-Dieu, Nantes, Frankreich
11UT Southwestern Medical Center, Dallas, USA
12A.O.U. Citta Della Salute e della Scienza di Torino, Torino, Italien
13Department of Hematology, Medical University of Lodz, Copernicus Memorial
Hospital, Ciolkowskiego, Polen
14Celgene International Sàrl, a Bristol Myers Squibb Company, Boudry, Schweiz
15Bristol Myers Squibb, Princeton, USA
16Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology,
Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA
Background: Patients (pts) with newly diagnosed multiple myeloma
(MM) are routinely treated with lenalidomide (LEN) until disease pro-
gression, thus frequently developing LEN-refractory MM at relapse. Pts
with RRMM treated with POM, BORT, and DEX (PVd) at rst relapse in
OPTIMISMM (phase 3, NCT01734928) had a signicantly longer median
progression-free survival (20.7 vs 11.6 mo) vs BORT and DEX (Vd); all
pts were LEN-exposed and 57% were LEN refractory (Richardson et al.
Lancet Oncol 2019;20:781–94). Here we report a safety analysis of treat-
ment-emergent adverse events (TEAE) in the events of interest (EOI) cat-
egory for PVd vs Vd administered at rst relapse in OPTIMISMM.
Methods : In 21-day cycles, pts with RRMM received PVd or Vd (1:1).
Key eligibility criteria included ≥ 2 cycles of prior LEN; LEN-refractory
pts were allowed. AEs were graded (NCI CTCAE v4.0) and summarized
by system organ class and preferred term.
Result: e safety analysis included 221/559 pts (PVd, n = 111; Vd, n =
110) who had 1 prior line of therapy and received ≥ 1 dose of study drug.
Median duration of treatment was longer in the PVd vs Vd arm: 47.4 vs
27.1 weeks. e most common grade (Gr) 3/4 TEAE EOIs were neutrope-
nia (24.4%), infections and infestations (22.2%), and thrombocytopenia
(20.4%). Gr 3/4 TEAE EOIs more common in the PVd vs Vd arm included
neutropenia (36.9% vs 11.8%), infections and infestations (28.8% vs
15.5%), and peripheral neuropathy (PNP; 11.7% vs 4.5%). Onset of TEAE
EOIs were mostly in early cycles and mainly managed with dose reduc-
tions/interruptions. POM discontinuations due to ≥ 1 TEAE EOI of any
grade were low (9.0%). Infections and infestations were the primary cause
of PVd dose interruptions (54.1%). PNP was the most common TEAE
EOI leading to dose reduction (32.4%) and drug discontinuation (16.2%)
with PVd.
Discussion: e safety prole of PVd at rst relapse in pts with RRMM
aligns with previous reports.
Conclusion: TEAE EOIs generally occurred in early treatment cycles and
were manageable with dose modications or appropriate treatment.
Source:
1. Weisel K, et al. HemaSphere 2021;5:e464–5. EP988
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
166
Acalabrutinib ± Obinutuzumab vs Obinutuzumab +
Chlorambucil in Treatment-Naive Chronic Lymphocytic
Leukemia: 5-Year Follow-Up of ELEVATE-TN
Uwe Martens1; Je Sharman2; Miklos Egyed3; Wojciech Jurczak4;
Alan P. Skarbnik5; Manali Kamdar6; Talha Munir7; Laura Maria Fogliatto8;
Yair Herishanu9; Versha Banerji10; George Follows11; Patricia Walker12;
Karin Karlsson13; Paolo Ghia14; Ann Janssens15; Emmanuelle Ferrant16;
Veerendra Munugalavadla17; Ting Yu17; Min Hui Wang17;
Jennifer Woyach18
1SLK-Kliniken GmbH Heilbronn, Heilbronn, Deutschland
2Willamette Valley Cancer Institute and Research Center, Eugene, OR, USA
3Somogy County Mór Kaposi General Hospital, Kaposvár, Ungarn
4Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, Polen
5Novant Health Cancer Institute, Charlotte, North Carolina, USA
6University of Colorado Cancer Center, Aurora, Colorado, USA
7Haematology, Haematological Malignancy Diagnostic Service (HMDS), St.
Jamess Institute of Oncology, Leeds, Vereinigtes Königreich
8Hospital de Clinicas de Porto Alegre, Porto Alegre, Brasilien
9Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
10University of Manitoba and CancerCare Manitoba, Winnipeg, MB, Kanada
11Department of Haematology, Addenbrookes Hospital NHS Trust, Cambridge,
Vereinigtes Königreich
12Peninsula Health and Peninsula Private Hospital, Frankston, Melbourne,
Australien
13Skåne University Hospital, Lund, Schweden
14Università Vita-Salute San Raaele and IRCCS Ospedale San Raaele, Milano,
Italien
15University Hospitals Leuven, Leuven, Belgien
16Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Service dHématologie
Clinique, Pierre-Bénite, Frankreich
17AstraZeneca, South San Francisco, CA, USA
18The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
Background: For ELEVATE-TN (NCT02475681), we previously reported
superior ecacy of acalabrutinib (A) ± obinutuzumab (O) vs O + chlo-
rambucil (Clb) in patients (pts) with treatment-naive (TN) chronic
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts166
lymphocytic leukemia (CLL) at 28.3 and 46.9 months (mo) median fol-
low-up. As submitted to ASCO 2022, we now report results from a 5-year
(y) update.
Methods: Pts were randomized to A+O, A, or O+Clb. Pts who progressed
on O+Clb could cross over to A monotherapy. Investigator-assessed
(INV) progression-free survival (PFS), INV overall response rate (ORR),
overall survival (OS), and safety were evaluated.
Result: A total of 535 pts (A+O, n=179; A, n=179; O+Clb, n=177) had a
median age of 70 y. At a median follow-up of 58.2 mo (range, 0.0–72.0;
data cuto Oct 1, 2021), median PFS was not reached (NR) (hazard
ratio [HR]: 0.11) for A+O and A (HR: 0.21) vs 27.8 mo for O+Clb (both
P<0.0001). Estimated 60-mo PFS rates were 84% (A+O), 72% (A), and
21% (O+Clb). Median OS was NR in any treatment arm, and signicantly
longer in the A+O vs O+Clb arms (HR: 0.55; P=0.0474); estimated 60-mo
OS rates were 90% (A+O), 84% (A), and 82% (O+Clb). ORR was signi-
cantly higher with A+O (96%; 95% CI 92–98) and A (90%; 85–94) vs
O+Clb (83%; 77–88; P<0.0001 [A+O], P=0.0499 [A]). Complete response
(CR)/ CR with incomplete hematologic recovery (CRi) rates were higher
with A+O (29%/3%) vs O+Clb (13%/1%); 13%/1% had CR/CRi with
A; CR increased since the interim analysis (previously 21% [A+O] and
7% [A]). Treatment is ongoing in 65% (A+O) and 60% (A) of pts; the
most common reasons for treatment discontinuation were adverse events
(AEs) (17% [A+O], 16% [A], 14% [O+Clb]) and progressive disease (6%,
10%, 2%, respectively). Crossover from O+Clb to A occurred in 72 (41%)
patients; 25% of these pts discontinued A (10% due to AEs and 11% due
to progressive disease).
Discussion and Conclusion: Aer a 5-y follow-up, ecacy and safety of
A+O and A monotherapy were maintained, with signicantly longer OS
in the A+O arm compared with O+Clb.
Sponsor: Acerta Pharma BV; AstraZeneca
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
239
Eectiveness and Safety of Sandoz Biosimilar Rituximab
(Rixathon [c]) in Patients with DLBCL: 24-Month Evidence from
the REFLECT Study
Manfred Welslau1; Thomas Wol2; Burkhard Joerg Otremba3;
Julian Topaly4; Boris Kubuschok5; Galyna Bryn6
1Chefarzt MK IV - Klinikum Aschaenburg, Aschaenburg, Deutschland
2Onkologie Lerchenfeld, Hamburg, Deutschland
3Onkologische Praxis, Oldenburg-Delmenhorst, Oldenburg, Deutschland
4MVZ Klinikum Osnabrück GmbH, Osnabrück, Deutschland
5Medizinische Klinik und Comprehensive Cancer Center, Universitätsklinikum
Augsburg Stenglinstr, Augsburg, Deutschland
6Sandoz Group, a Novartis Division, Holzkirchen, Deutschland
Background: Sandoz rituximab (SDZ-RTX; Rixathon®), a biosimilar,
was approved in Europe for all indications of the reference rituximab.
REFLECT is a real-world, multicentre non-interventional trial and is the
rst prospective post-approval study of SDZ-RTX in combination with
CHOP as curative therapy for diuse large B-cell lymphoma (DLBCL).
Objective: To evaluate the 2-year eectiveness and safety of SDZ-RTX
in 1st line treatment of DLBCL. Eectiveness was measured by complete
response (CR) rate as primary endpoint.
Methods: Treatment-naïve, CD20+ adult patients (aged ≥18 years) with
DLBCL, eligible for therapy with rituximab-CHOP were treated with
SDZ-RTX-CHOP every 2 to 3 weeks for 6–8 cycles according to product
label. CR was assessed as the best result by the treating physician.
No imputation for missing data was used; endpoints were summarized
descriptively.
Results: A total of 169 patients (52.1% women, mean [SD] age 67.3 [13.4]
years) with DLBCL were included. At baseline most patients (80.5%) had
an Eastern Cooperative Oncology Group (ECOG) performance score of
0/1. A total of 100 (59.2%) patients completed the 24-month observation
period. Overall response was achieved in 160 (94.7%) patients (95%CI:
90.1–97.5). A majority, 110 (65.1%) patients, achieved CR (95%CI:
57.4–72.3) and 50 (29.6%) patients achieved partial response (95%CI:
22.8–37.1). One year progression free survival (PFS) was 84.9% (95%CI:
78.2–89.6), while 2 years PFS was 78.5% (95%CI: 70.9–84.4). Median PFS
was not reached. A total of 143 (84.6%) patients experienced at least one
AE; most common were anaemia (24.3%), fatigue (20.7%), polyneuropa-
thy (17.2%) and nausea (12.4%).
Conclusion: is study reconrms that 1st line treatment of CD20+
DLBCL with R-CHOP using SDZ-RTX (Rixathon [c]) is eective over a
24-months observation period with no unexpected safety signals.
Disclosure Statement: e authors declare the following:
1. Manfred Welslau: Dr. Welslau reports engagement other from Novartis, during
the conduct of the study; consultation to AMGEN, Bristol-Myers Squibb,
Celgene, GILEAD, HEXAL, Janssen, Lilly, medac, Roche, SANOFI, and
received honorariums from AMGEN, astellas, AstraZeneca, Celgene, GILEAD,
HEXAL, Janssen, Lilly, Roche, SANOFI, outside the submitted work.
2. Galyna Bryn: Dr. Bryn is employed by Sandoz, during the conduct of the study.
252
Final results of IDELA PASS: A prospective non-interventional
post authorization safety study of idelalisib in Germany
Manuela Hoechstetter1; Wolfgang Ulrich Knauf2; Silvia Dambacher3;
Nike Hucke3; Anna van Troostenburg3; Heribert Ramroth3;
Wolfgang Abenhardt4; Mathias Rummel5
1München Klinik Schwabingen, Klinik für Hämatologie, Onkologie,
Immunologie, Palliativmedizin, Infektiologie und Tropenmedizin, München,
Deutschland
2Onkologie Bethanien Frankfurt am Main, Centrum für Hämatologie und
Onkologie, Frankfurt am Main, Deutschland
3Gilead Sciences GmbH, Martinsried bei München, München, Deutschland
4Onco Consult Gilching GmbH, Gilching, Deutschland
5Universitätsklinikum Gießen und Marburg, Schwerpunktabteilung für
Hämatologie (Med. Klinik IV), Gießen, Deutschland
Background: In clinical studies idelalisib (rst-in-class PI3Kδ-inhibitor)
demonstrated signicant ecacy in patients with CLL and FL. On this
basis idelalisib is indicated in combination with rituximab for the treat-
ment of adult patients with chronic lymphocytic leukaemia (CLL) who
received at least one prior therapy or as 1L treatment in the presence of
del(17p) or TP53mut in patients not eligible for any other therapy and as
monotherapy for the treatment of adult patients with follicular lymphoma
(FL) refractory to two prior lines of treatment. Here we show the nal
results of Post-Authorization Safety Study (PASS) prospectively investi-
gating safety and eectiveness in routine clinical practice in Germany.
Methods: A prospective, two-cohort, multicenter, PASS reporting safety
and eectiveness. Inclusion of patients was based on the physicians deci-
sion and in accordance with the European SmPC. Descriptive statistics
were used for data analysis.
Result: is nal analysis shows data from 147 patients (125 CLL; 22
FL) with a median age of 74 (43-92) years. Most patients presented with
≥one comorbidity and advanced disease status at baseline. With a median
observation time of 9.2 (7.0-11.3) months the median OS was not reached
(NR) for either patient population including CLL patients with and with-
out del(17p) and/or TP53mut. In patients with CLL the ORR was 70%, for
FL 36%. Median PFS for FL was 3.5 (2.3 – 7.7) months, whereas NR for
CLL. Subgroup analysis in the CLL cohort of PFS by numbers of prior reg-
imens suggests that idelalisib treatment in earlier lines of therapy results
in a longer PFS. e most frequently reported ADR in CLL and FL cohort
was diarrhoea with 28%/36.4%.
Discussion: Real-world eectiveness in this PASS conrms clinical e-
cacy of idelalisib in CLL. e collected safety data and the pattern of ADRs
in this study reect the patterns of ADRs from previous clinical trials with
idelalisib.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 167
Conclusion: e results demonstrate that idelalisib is a potent treatment
for patients with CLL and FL with a manageable safety prole in routine
clinical practice.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
339
PET-Guided Treatment in Patients with Early-Stage Favorable
Hodgkin Lymphoma: Follow-up Analysis of the HD16 Trial by the
German Hodgkin Study Group
Anne Sophie Jacob1; Michael Fuchs1; Helen Kaul1; Carsten Kobe2;
Thomas Pabst3,4; Richard Greil5,6; Dennis Eichenauer1; Max Topp6;
Marianne Just7; Bernd Hertenstein8; Valdete Schaub9;
Martin Vogelhuber10; Josée M Zijlstra11; Annette Pluetschow1;
Christian Baues12; Andreas Rosenwald13; Markus Dietlein2;
Peter Borchmann1; Andreas Engert1
1Department I of Internal Medicine, Center for Integrated Oncology Aachen,
Bonn, Cologne, Düsseldorf, Faculty of Medicine and University of Cologne,
German Hodgkin Study Group, Köln, Deutschland
2Department of Nuclear Medicine, Faculty of Medicine and University of
Cologne, Köln, Deutschland
3Inselspital, Universitätsspital Bern, Bern, Schweiz
4Swiss Group for Clinical Cancer Research (SAKK), Bern, Schweiz
5IIIrd Medical Department, Paracelsus Medical University and Salzburg
Cancer Research Institute-CCCIT, Cancer Cluster Salzburg and AGMT
(Arbeitsgemeinschaft Medikamentöse Tumortherapie), Salzburg, Österreich
6Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg,
Deutschland
7Onkologische Schwerpunktpraxis Bielefeld, Bielefeld, Deutschland
8Klinikum Bremen-Mitte, Department of Internal Medicine I, Bremen,
Deutschland
9Universitätsklinikum Tübingen, Medizinische Klinik II, Tübingen, Deutschland
10Medizinische Klinik III, Uniklinik Regensburg, Regensburg, Deutschland
11Amsterdam UMC, Dept Hematology, Vrije Universiteit, Cancer Center
Amsterdam, Amsterdam, Niederlande
12Department of Radiooncology and Cyberknife Center, Faculty of Medicine and
University of Cologne, Cologne, Köln, Deutschland
13Institute of Pathology , Julius-Maximilians-Universität Würzburg, Würzburg,
Deutschland
Background: e primary analysis of HD16 revealed that in the treat-
ment of early-stage favorable Hodgkin lymphoma (HL), consolidation
radiotherapy aer chemotherapy cannot be omitted without a clinically
signicant loss of tumor control.
Methods: Between 11/2009 and 12/2015, 1150 patients aged 18-75 years
with newly diagnosed early-stage favorable HL were randomized between
standard combined-modality treatment (CMT) (2xABVD followed by
PET/CT-based staging [PET-2] and 20Gy involved-eld radiotherapy)
and PET-2-guided treatment (omitting radiotherapy aer negative PET-2,
i.e. Deauville score [DS]<3). HD16 aimed at excluding inferiority of PET-
2-guided treatment in terms of a HR≥3.01 for PFS in the PET-2-negative
per-protocol cohort and assessing the prognostic impact of PET-2 among
patients receiving CMT. We now aimed at repeating analyses with longer
follow-up and adding long-term safety data.
Result: Aer a median follow-up of 64 months, PET-2-negative patients
had ve-year PFS rates of 94.2% (95% CI 91.6–96.9) aer CMT (n=328)
and 86.7% (82.5–90.9) aer ABVD alone (n=300; HR=2.05 [1.20-3.51];
p=0.0072). Five-year overall survival was 98.3% (96.9–99.8) and 98.8%
(97.4–100), respectively (p=0.14), with 4/12 documented deaths caused
by second primary malignancies and only 1 by HL. Among patients who
had received CMT, PFS was superior in PET-2-negative (n=353; 5-year
PFS 94.0% [91.4-96.6]) compared with PET-2-positive patients (n=340;
90.3% [86.9-93.6]; p=0.012). e dierence was more pronounced when
the more common cut-o of DS4 was used (DS1-3: n=571; 94.0% [91.9-
96.0] vs. DS≥4: n=122; 83.6% [76.6-90.6]; p<0.0001).
Conclusion: We conclude that radiotherapy cannot be omitted from the
treatment of early-stage favorable HL without a clinically relevant and
statistically signicant loss of ecacy. We could not observe any disad-
vantage of standard CMT over PET-guided therapy in terms of acute or
late toxicities.
Disclosure Statement: e authors declare no conict of interest.
349
Pirtobrutinib; A Next Generation; Highly Selective; Non-covalent
BTK Inhibitor In Previously Treated CLL/SLL: Updated Results
From The Phase 1/2 BRUIN Study
John M. Pagel1; Catherine C. Coombs2; Nirav N. Shah3; Nicole Lamanna4;
Ewa Lech-Maranda5; Toby A. Eyre6; Jennifer A. Woyach7;
William G. Weirda8; Chan Y. Cheah9; Lindsey E. Roeker10; Manish R. Patel11;
Bita Fakhri12; Minal A. Barve13; Constantine Tam14; David Lewis15;
James N. Gerson16; Alvaro J. Alencar17; Paolo Ghia18; Stephen J. Schuster16;
Matthew S. Davids19; Jennifer R. Brown19; Wojciech Jurczak20;
Anthony R. Mato21
1Seattle, Swedish Cancer Institute, Seattle, USA
2Chapel Hill, University of North Carolina at Chapel Hill, Chapel Hill, USA
3Milwaukee, Medical College of Wisconsin, Milwaukee, USA
4New York City, Herbert Irving Comprehensive Cancer Center, Columbia
University, New York City, USA
5Warsaw, Institute of Hematology and Transfusion Medicine, Warsaw, Polen
6Oxford, Oxford University Hospitals NHS Foundation Trust, Churchill Cancer
Center, Oxford, Vereinigtes Königreich
7Columbus, The Ohio State University Comprehensive Cancer Center,
Columbus, USA
8Texas, MD Anderson Cancer Center, Texas, USA
9Perth, Linear Clinical Research and Sir Charles Gairdner Hospital, Perth,
Australien
10New York City, Memorial Sloan Kettering Cancer Center, New York City, USA
11Sarasota, Florida Cancer Specialists/Sarah Cannon Research Institute,
Sarasota, USA
12San Francisco, University of California San Francisco, San Francisco, USA
13Dallas, Mary Crowley Cancer Research, Dallas, USA
14Melbourne, Peter MacCallum Cancer Center, Royal Melbourne Hospital, and
University of Melbourne, Melbourne, Australien
15Plymouth, University Hospitals Plymouth NHS, Plymouth, Vereinigtes
Königreich
16Philadelphia, University of Pennsylvania, Philadelphia, USA
17Miami, University of Miami Miller School of Medicine, Miami, USA
18Mailand, Università Vita-Salute San Raaele and IRCCS Ospedale San Raaele,
Mailand, Italien
19Boston, Dana-Farber Cancer Institute and Harvard Medical School, Boston, USA
20Krakow, Maria Sklodowska-Curie National Research Institute of Oncology,
Krakow, Polen
21Memorial Sloan Kettering Cancer Center, New York City, USA
Background: Covalent BTK inhibitors (BTKi) have transformed the man-
agement of chronic lymphocytic leukemia/small lymphocytic lymphoma
(CLL/SLL) although many patients (pts) require additional treatment. In
a phase 1/2 BRUIN study, pirtobrutinib a highly selective, non-covalent
BTKi achieved pharmacokinetic exposures that exceeded its BTK IC96 at
trough, was well tolerated and demonstrated promising ecacy in CLL/
SLL pts despite prior therapy, number of prior lines of therapy, or BTK
C481 mutation status (Mato et al. Lancet 2021;397,10277:892-901).
Methods: BRUIN is a multicenter phase 1/2 study (NCT03740529) of oral
pirtobrutinib monotherapy in pts with advanced B-cell malignancies. e
primary objective for phase 1 was the recommended phase 2 dose (RP2D)
and the primary objective of phase 2 was overall response rate (ORR).
Results: As of 27 September 2020, 323 pts (170 CLL/SLL, 61 MCL, 26
WM, 26 DLBCL, 13 MZL, 12 FL, 9 RT, and 6 other NHL) were treated on
7 dose levels (25-300mg QD). Median age was 69 (range 36-88) years for
CLL/SLL pts. Median number of prior lines of therapy was 3 (range 1-11).
No DLTs were reported, MTD was not reached (n=323) and 200mg QD
was selected as the RP2D. e most frequent treatment-emergent adverse
events regardless of attribution or grade seen in >10% of pts (n=323) were
fatigue (20%), diarrhea (17%) and contusion (13%). e most common
adverse event of grade ≥3 was neutropenia (10%). Five (1%) pts dis-
continued due to treatment-related adverse events. e ORR was 63%
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts168
(95% CI 55-71) among the 139 ecacy evaluable CLL/SLL pts with 69
PRs (50%), 19 PR-Ls (14%), 45 SDs (32%), and 1 PD (1%), and 5 (4%)
discontinued prior to rst response assessment. Median follow up time
was 6 months (range 0.16-17.8+).
Conclusion: Pirtobrutinib was well tolerated and exhibited a wide ther-
apeutic index. Pirtobrutinib demonstrated promising ecacy in heavily
pretreated CLL/SLL pts following multiple prior lines of therapy, includ-
ing a covalent BTKi and a BCL2 inhibitor. Updated data, from ~100 new
pts with CLL and an additional 10 months since the prior data cut will be
presented.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
392
A population based study of treatment of Hodgkin Lymphoma
in older patients with data of the Cancer Registry
of Baden-Württemberg (BW); Germany
Claudia Winzler; Irina Surovtsova; Daria Kokh; Philipp Morakis
Klinische Landesregisterstelle, Krebsregister Baden-Württemberg, Stuttgart,
Deutschland
Introduction: Hodgkin Lymphoma (HL) is a treatable condition with a
5 year survival rate of 80-90%. Older age is an adverse prognostic factor,
which might be related to comorbidities, tumour biology and to therapy
choice. Physicians have to treat a potentially curative lymphoma but pro-
tect their patients from unacceptable toxicities.
Objective: e purpose of the present study was to analyse the primary
treatment of incident classical HL (cHL) in older patients aged > 60 years
compared to younger ones by using data of the Cancer Registry of BW.
Methods: Adult patients with cHL diagnosed between 2016-2020 were
included (approximately 1300 patients; about 25% > 60 years old). Primary
therapy dened as the rst systemic therapy started within 3 months and
radiotherapy within 6 months was compared between patients aged 18-60
years and those aged > 60 years. Chemotherapy regimens were catego-
rized as standard (ABVD and BEACOPP), non-standard, single agent and
no treatment. Dierences in gender, histology, Ann Arbor stage, out-of
hospital therapy and timing of primary therapy were analysed.
Results: e analysis shows that tumours in older patients are more fre-
quently of mixed cellularity and non-specied histology and diagnosed at
a later stage (III or IV). Compared to younger patients, radiotherapy was
less applied. In the elderly, chemotherapy was performed less oen with
standard protocols. BEACOPP is less used compared to young patients.
About 35% of older patients were treated with non-standard protocols.
Among non-standard protocols, AVD, Brentuximab-AVD and PVAG
were most commonly used. e remaining ones were variable other pro-
tocols or single agents.
Conclusions: e data show dierent treatment modalities for patients
with cHL aged > 60 years compared to younger ones. Dierences are
found also for histology and stage. Higher relapse and death rates, as
reported from international studies, might not be due only to age, but also
to tumour biology, tumour extension at diagnosis and therapy modalities.
Disclosure Statement: e authors declare no conict of interest.
411
Characterization of Bruton Tyrosine Kinase Inhibitor
(BTKi)-Related Adverse Events in a Head-to-Head Trial of
Acalabrutinib Versus Ibrutinib in Previously Treated Chronic
Lymphocytic Leukemia (CLL)
Stephan Stilgenbauer1; John F. Seymour2; John C. Byrd3; Peter Hillmen4;
Paolo Ghia5; Arnon P. Kater6; Asher Chanan-Khan7; Richard R. Furman8;
Susan O’brien9; Jennifer R. Brown10; Anthony Mato11;
Nataliya Kuptsova-Clarkson12; Paulo Miranda12; Dennis Wagner13;
Kara Higgins14; Sophia Sohoni14; Wojciech Jurczak15
1University of Ulm, Internal Medicine III, Ulm, Deutschland
2Peter MacCallum Cancer Centre, Royal Melbourne Hospital, and University of
Melbourne, Victoria, Australien
3The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
4St. Jamess University Hospital, Leeds, Vereinigtes Königreich
5Università Vita-Salute San Raaele and IRCCS Ospedale San Raaele, Milano,
Italien
6Amsterdam University Medical Center, Amsterdam, on behalf of Hovon,
Niederlande
7Mayo Clinic Jacksonville, Jacksonville, FL, USA
8Weill Cornell Medicine, New York Presbyterian Hospital, New York, NY, USA
9Chao Family Comprehensive Cancer Center, University of California-Irvine,
Irvine, CA, USA
10Dana-Farber Cancer Institute, Boston, MA, USA
11University of Pennsylvania, Philadelphia, PA, USA
12AstraZeneca, Gaithersburg, MD, USA
13AstraZeneca, Mississauga, Ontario, Kanada
14AstraZeneca, South San Francisco, CA, USA
15Maria Sklodowska-Curie National Research Institute of Oncology, Krakow,
Polen
Background: As submitted to ASH 2021, we report additional data
of a phase 3 head-to-head trial of acalabrutinib (A) vs ibrutinib (Ibr)
(NCT02477696) to further characterize BTKi-related adverse events
(AEs) and the safety prole of A and Ibr.
Methods: Patients (Pt) received oral A BID or Ibr QD until disease pro-
gression or unacceptable toxicity. Overall incidence, exposure-adjusted
(exp-adj) incidence, and exp-adj time with event were assessed for the
most common BTKi-related AEs. Atrial brillation (ab)/utter, hyper-
tension, and bleeding events were further characterized by time to onset,
cumulative incidence, Pt subgroup, and AE management.
Result: A total of 533 Pt (A, n=268; Ibr, n=265) were randomized; median
treatment exposures were 38.3 and 35.5 months (mo), respectively.
Among events of clinical interest, incidences of any-grade ab/utter,
hypertension, bleeding, diarrhea, arthralgia, contusion, urinary tract
infection (UTI), back pain, muscle spasms and dyspepsia were statisti-
cally higher with Ibr with higher exp-adj incidence and exp-adj time with
event (except for UTI). Incidences and exp-adj time with event of head-
ache and cough were statistically higher with A. Total exp-adj time with
event for all any-grade AEs was 37% higher with Ibr. Any-grade ab/ut-
ter, hypertension and bleeding events showed lower cumulative incidence
with A at 6, 12, 18 and 24 mo, and occurred less frequently in subgroups
of age and prior line of therapy. Among Pt without prior history, any grade
ab/utter and hypertension occurred less frequently and showed a 63%
and 77% reduction rate favoring A, respectively. Among all Pt, concom-
itant medication use for ab/utter was less common for A (8%) vs Ibr
(14%), with antithrombotic use reported in 5% vs 9% of Pt, respectively.
Concomitant medication use for hypertension was less common for A
(5%) vs Ibr (19%).
Discussion and Conclusion: In this head-to-head trial of BTKis in CLL,
event-based analyses demonstrated a higher BTKi-related toxicity bur-
den with Ibr, with a lower impact of CV-related toxicity with A across
subgroups.
Sponsor: Acerta Pharma BV; AstraZeneca
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 169
414
Acalabrutinib vs Rituximab Plus Idelalisib or Bendamustine in
Relapsed/Refractory Chronic Lymphocytic Leukemia: ASCEND
Results at ~4 Years of Follow-up
Manfred Welslau1; Wojciech Jurczak2; Andrzej Pluta3; Malgorzata Wach4;
Daniel Lysak5; Martin Šimkovič6; Irina Kryachok7; Arpad Illes8; Javier De la
Serna9; Sean Dolan10; Philip Campbell11; Gerardo Musuraca12; Abraham
Jacob13; Eric Avery14; Jae Hoon Lee15; Ganna Usenko16; Min Hui Wang17;
Ting Yu17; Paolo Ghia18
1MVZ am Klinikum Aschaenburg, Aschaenburg, Deutschland
2Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, Polen
3Department of Hematological Oncology, Oncology Specialist Hospital,
Brzozow, Polen
4Department of Hemato-Oncology and Bone Marrow Transplantation, Medical
University of Lublin, Lublin, Polen
5Fakultní Nemocnice Plzen, Pilsen, Tschechische Republik
6University Hospital Hradec Kralove, Charles University, Hradec Kralove,
Tschechische Republik
7National Cancer Institute, Kiev, Ukraine
8University of Debrecen, Debrecen, Ungarn
9Hospital Universitario 12 de Octubre, Madrid, Spanien
10Saint John Regional Hospital, University of New Brunswick, New Brunswick,
Kanada
11Barwon Health, University Hospital Geelong, Geelong, Victoria, Australien
12Istituto Scientico Romagnolo per lo Studio e la Cura dei Tumori, Meldola,
Italien
13Royal Wolverhampton Hospital National Health Service Trust, Wolverhampton,
Vereinigtes Königreich
14Nebraska Hematology Oncology, Lincoln, NE, USA
15Gachon University Gil Medical Center, Incheon, Republik Korea
16City Clinical Hospital, No. 4 DCC, Dnipro, Ukraine
17AstraZeneca, South San Francisco, CA, USA
18Università Vita-Salute San Raaele and IRCCS Ospedale San Raaele, Milano,
Italien
Background: In primary analysis of ASCEND (median follow-up 16.1
months (mo)), acalabrutinib (A) showed superior ecacy with acceptable
tolerability prole vs idelalisib (Id) + rituximab (R) (IdR) or bendamus-
tine (B) + R (BR) in pt with relapsed/refractory (R/R) chronic lympho-
cytic leukemia (CLL).1 We report the results at ~4 years (y) of follow-up
which were rst submitted to ASCO 2022.
Methods: In this multicenter, open-label phase 3 study (NCT02970318),
pt with R/R CLL received A until progression or unacceptable toxicity or
investigator’s (INV) choice of IdR (Id: until progression or unacceptable
toxicity; R: 8 infusions) or BR (6 cycles). Crossover to A was permitted
in pt who progressed on IdR/BR. Progression-free survival (PFS), overall
survival (OS), overall response rate (ORR), and safety were assessed.
Result: 310 pt (A, n=155; IdR, n=119; BR, n=36) were randomized
(median age 67 y; del(17p) 15%, unmutated IGHV 74%, Rai stage 3/4
42%). At median follow-up of 46.5 mo (A) and 45.3 mo (IdR/BR), A sig-
nicantly prolonged INV-assessed PFS vs IdR/BR (median not reached
(NR) vs 16.8 mo; P<0.0001); 42-mo PFS rates were 62% for A vs 19% for
IdR/BR. In pt with del(17p), median PFS was NR (A) vs 13.8 mo (IdR/
BR; P<0.0001). In pt with unmutated IGHV, median PFS was NR (A) vs
16.2 mo (IdR/BR; P<0.0001). Median OS was NR in both arms; 42-mo
OS rates were 78% (A) vs 65% (IdR/BR). ORR was 83% (A) vs 84% (IdR/
BR) (ORR + partial response with lymphocytosis: 92% (A) vs 88% (IdR/
BR)). Adverse Events led to drug discontinuation in 23% of A, 67% of
IdR, and 17% of BR pt. Events of clinical interest (A vs IdR/BR) included
all-grade atrial brillation/utter (8% vs 3%), all-grade hypertension (8%
vs 5%), all-grade major hemorrhage (3% vs 3%), and grade ≥3 infections
(29% vs 29%).
Discussion and Conclusion: At ~4 y of follow-up, A maintained ecacy
compared with standard-of-care regimens and a consistent tolerability
prole in R/R CLL.
Indication of source:
1 Ghia et al. J Clin Oncol. 2020;38:2849-2861
Sponsor: Acerta Pharma BV; AstraZeneca
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
516
Pirtobrutinib, A Next Generation, Highly Selective,
Non-covalent BTK Inhibitor In Previously Treated Mantle Cell
Lymphoma: Updated Results From The Phase 1/2 BRUIN Study
Nirav N. Shah1; Alvaro J. Alencar2; James N. Gerson3; Manish R. Patel4;
Bita Fakhri5; Wojciech Jurczak6; Xuan Tan7; Katharine Lewis7;
Timothy Fenske1; Catherine C. Coombs8; Ian Flinn9; David Lewis10;
Steven Le Gouill11; M. Lia Palomba12; Jennifer Woyach13; John M. Pagel14;
Nicole Lamanna15; Johnathon B. Cohen16; Minal A. Barve17; Paolo Ghia18;
Toby A. Eyre19; Anthony R. Mato12; Chan Y. Cheah7; Michael L. Wang20
1Milwaukee, Medical College of Wisconsin, Milwaukee, USA
2Miami, Sylvester Comprehensive Cancer Center, Miami, USA
3Philadelphia, University of Pennsylvania, Philadelphia, USA
4Sarasota, Florida Cancer Specialists/Sarah Cannon Research Institute,
Sarasota,USA
5San Francisco, University of California San Francisco, San Francisco, USA
6Krakow, Maria Sklodowska-Curie National Research Institute of Oncology,
Krakow, Polen
7Perth, Linear Clinical Research and Sir Charles Gairdner Hospital, Perth,
Australien
8Chapel Hill, University of North Carolina at Chapel Hill, Chapel Hill, USA
9Nashville, Sarah Cannon Research Institute, Nashville, USA
10Plymouth, University Hospitals Plymouth NHS, Plymouth, Vereinigtes
Königreich
11Nantes, Service dhématologie clinique du CHU de Nantes, INSERM CRCINA
Nantes-Angers, NeXT Université de Nantes, Nantes, Frankreich
12New York City, Memorial Sloan Kettering Cancer Center, New York City, USA
13Columbus, The Ohio State University Comprehensive Cancer Center,
Columbus, USA
14Seattle, Swedish Cancer Institute, Seattle, USA
15New York City, Herbert Irving Comprehensive Cancer Center, Columbia
University, New York City, USA
16Atlanta, Winship Cancer Institute, Emory University, Atlanta, USA
17Dallas, Mary Crowley Cancer Research, Dallas, USA
18Mailand, Università Vita-Salute San Raaele and IRCCS Ospedale San Raaele,
Mailand, Italien
19Oxford, Oxford University Hospitals NHS Foundation Trust, Churchill Cancer
Center, Oxford, Vereinigtes Königreich
20Texas, MD Anderson Cancer Center, Texas, USA
Background: Covalent BTK inhibitors (BTKi) have transformed the man-
agement of mantle cell lymphoma (MCL) although a majority of patients
(pts) on these agents require additional treatment. In a phase 1/2 BRUIN
study, pirtobrutinib a highly selective, non-covalent BTKi achieved phar-
macokinetic exposures that exceeded its BTK IC96 at trough, was well
tolerated and demonstrated promising ecacy in heavily pretreated,
poor-prognosis MCL pts, most of whom had prior treatment with a cova-
lent BTKi (Mato et al. Lancet 2021;397, 10277:892-901).
Methods: BRUIN is a multicenter phase 1/2 study (NCT03740529) of oral
pirtobrutinib monotherapy in pts with advanced B-cell malignancies. e
primary objective for phase 1 was to determine the recommended phase
2 dose (RP2D) and the primary objective of phase 2 was overall response
rate (ORR).
Results: As of 27 September 2020, 323 pts (170 CLL/SLL, 61 MCL, 26
WM, 26 DLBCL, 13 MZL, 12 FL, 9 RT, and 6 other NHL) were treated
on 7 dose levels (25-300mg QD).Median age was 69 (range 50-87) years
for MCL pts. Among the 61 MCL pts, median number of prior lines of
therapy was 3 (range, 1-8). No DLTs were reported and MTD was not
reached (n=323) and 200mg QD was selected as the RP2D. e most
frequent treatment-emergent adverse events regardless of attribution or
grade seen in >10% of pts (n=323) were fatigue (20%), diarrhea (17%)
and contusion (13%). e most common adverse event of grade ≥3 was
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts170
neutropenia (10%). At the ecacy cuto date, 52 prior BTKi treated MCL
pts were ecacy evaluable with an ORR of 52% (95% CI 38-66) with 13
CR (25%), 14 PR (27%), 9 SD (17%), 11 PD (21%), and 5 (10%) discontin-
uations prior to rst response assessment. Median follow up was 6 months
(range 0.7-18.3+).
Conclusion: Pirtobrutinib was well tolerated and exhibited a wide ther-
apeutic index. Pirtobrutinib demonstrated promising ecacy in heavily
pretreated, poor-prognosis MCL following multiple prior lines of therapy,
including a covalent BTKi. Updated data from ~60 new pts with MCL and
an additional 10 months since the prior data cut will be presented.
Disclosure Statement: e authors declare no conict of interest.
534
Iberdomide (IBER) in combination with dexamethasone (DEX)
and daratumumab (DARA), bortezomib (BORT), or carlzomib
(CFZ) in patients (pts) with relapsed/refractory multiple
myeloma (RRMM)
Stefan Knop1; Sagar Lonial2; Paul Richardson3; Rakesh Popat4;
Edward A. Stadtmauer5; Jeremy T. Larsen6; Albert Oriol7; Sundar
Jagannath8; Gordon Cook9; Ashraf Z. Badros10; Paula Rodriguez-Otero11;
David Siegel12; Tuong VI Nguyen13; Antonia DI Micco14; Alpesh Amin13;
Min Chen13; Elisabeth Kueenburg14; Niels W.C.J. van de Donk15
1Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg,
Deutschland
2Winship Cancer Institute, Emory University, Atlanta, GA, USA
3Dana-Farber Cancer Institute, Boston, MA, USA
4NIHR UCLH Clinical Research Facility, University College London Hospitals NHS
Foundation Trust, London, Vereinigtes Königreich
5University of Pennsylvania, Philadelphia, PA, USA
6Mayo Clinic, Scottsdale, AZ, USA
7Institut de Recerca contra la Leucèmia Josep Carreras and Institut Català
dOncologia, Hospital Germans Trias i Pujol, Badalona, Spanien
8The Mount Sinai Hospital, New York, NY, USA
9Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University
of Leeds, Leeds, Vereinigtes Königreich
10The University of Maryland Marlene and Stewart Greenebaum Comprehensive
Cancer Center, University of Maryland Medical Center, Baltimore, MD, USA
11Clínica Universidad de Navarra, CIMA, IDISNA, CIBERONC, Pamplona, Spanien
12Division of Multiple Myeloma, John Theurer Cancer Center, Hackensack
University Medical Center, Hackensack, NJ, USA
13Bristol Myers Squibb, Princeton, NJ, USA
14Celgene International Sàrl, a Bristol-Myers Squibb Company, Boudry, Schweiz
15Amsterdam University Medical Center, VU Amsterdam, Department of
Hematology, Cancer Center Amsterdam, Amsterdam, Niederlande
Background: Here we report results from CC-220-MM-001
(NCT02773030), an ongoing phase 1/2 study evaluating MTD/RP2D,
safety, and ecacy of IBER+DARA+DEX (IberDd), IBER+BORT+DEX
(IberVd), and IBER+CFZ+DEX (IberKd) in pts with RRMM.
Methods: Eligible pts received ≥ 2 (IberDd and IberKd cohorts) or ≥ 1
prior regimens (IberVd cohort), containing LEN/POM, and a PI. All pts
had progressed ≤ 60 days of last therapy. Escalating oral doses of IBER
were given day (D)1–21 of each 28-d cycle in the IberDd and IberKd
cohorts, D1–14 of each 21-D cycle in the IberVd cohort.
Result: As of April 8, 2021, 43 pts had received IberDd, 25 IberVd, and 9
IberKd. Median age was 67, 64, and 61 y, and median time since diagno-
sis was 7.35, 7.10, and 6.70 y in the IberDd, IberVd, and IberKd cohorts,
respectively. Exposure to prior regimens was heterogeneous and ≥ 33% pts
in the 3 cohorts were triple-class refractory. IBER doses ranged from 1.0 to
1.6 mg. Median follow-up was 4.17, 4.86, and 5.03 mo, 22 (51%), 6 (24%),
and 5 (56%) pts continue on treatment, and median cycles received were
4, 6, and 5 with IberDd, IberVd, and IberKd, respectively. Hematologic
grade 3‒4 TEAEs of interest included neutropenia (67%), leukopenia
(23%), anemia (21%), and febrile neutropenia (5%) with IberDd; neutro-
penia (28%) and thrombocytopenia (24%) with IberVd; and lymphope-
nia (44%) and neutropenia (33%) with IberKd. e ORR was 46% with
IberDd, 56% with IberVd, and 50% with IberKd. Median time to response
was 4.1 (4.0‒12.0), 3.6 (3.0‒13.1), and 4.1 (4.1‒8.1) wk in the IberDd,
IberVd, and IberKd cohorts, respectively. Median duration of response is
35.7 wk in the IberVd cohort (not reached in the other cohorts). RP2D
was determined at 1.6 mg in the IberDd cohort; dose evaluation continues
in the other cohorts.
Discussion: ese results support further development of IBER-based
regimens in MM, including initiation of phase 3 combination studies.
Conclusion: In pts with heavily pretreated RRMM, IberDd, IberVd,
and IberKd showed a manageable safety prole and promising ecacy.
Previously published in Lonial S, et al. HemaSphere 2021;5(S2):49.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
574
Response to vaccination against Covid-19-virus in patients
with hematologic malignancies with respect to diagnosis and
treatment
Christoph Losem1; Lars Galonska2; Eike Albers3
1TZN Tumorzentrum Niederrhein GmbH, Neuss, Deutschland
2MVZ Hämatologie - Onkologie im Rhein-Kreis, Neuss, Deutschland
3Labor Quade & Kollegen GmbH, Köln, Deutschland
Background: In patients with hematologic malignancies response to
Covid-19-vaccination is unpredictable because these patients were
excluded from clinical trials in the past.
Methods: We measured B-cell-response by means of Covid-S1-antibody
reaction (SARS-CoV-2 IgG, Siemens Atellica IM) at earliest 3 weeks aer
second vaccination with the BNT162b2. In some patients T-cell-response
is determined by a Covid-Quantiferon-test (QuantiFERON SARS-CoV-2,
Qiagen)
Result: Untill August 2021 results for Covid-S1-antibody-testing were
present in 89 patients. In 46 of these patients response to vaccination was
missing by means of antibody determination (no measurable antibodies
against S1-antigen). Patients with no response to vaccination were mainly
patients with B-cell-lymphoma but also patients with multiple myeloma
und chronic myelomonocytic leukemia. 56 of 89 patients were on or aer
therapy with CD20-antibodies, respectivley. 39 of these 56 Patients had no
response to vaccination.
Discussion: Most available data concerning response to vaccination
against Covid-19-virus in patients with hematologic malignancies relate
to chronic B-cell leukemia and Covid-S1-antibody response. We present
single institution data of a variety of malignant hematologic diseases and
evalutate T-cell-response additionally.
Conclusion: Patients with hematologic malignancies and treatment with
CD20-abtibodies have a very high risk not to respond to vaccination
against Covid-19-virus. Since vaccination and testing has not nished yet
in our patients we will present updated results on response to vaccination
with respect to hematologic diagnosis, total dose of and intervall to CD20-
antibody-therapy on DKK-meeting in 2022.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 171
638
The eects of switching anti-CD20 antibodies on treatment
response and outcome for patients with B-Non-Hodgkin
lymphomas: A single-center retrospective data analysis
Constantin Bartzke; Claudia Baldus; Christiane Pott
Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik für Innere Medizin
II mit den Schwerpunkten Hämatologie und Onkologie, Kiel, Deutschland
Background: With the approval of rituximab biosimilars, a switch from
rituximab to anti-CD20 biosimilar can occur during treatment of B-cell
lymphomas (B-NHL). Only few data report whether an antibody switch
impacts on treatment response and prognosis. In this retrospective obser-
vational study, we aimed to evaluate response and outcome in B-NHL
aer switching from reference rituximab to a biosimilar.
Methods: B-NHL patients (pts.) who received an anti-CD20 antibody
treatment (January 2017 - December 2018) were evaluated regarding treat-
ment response to immunochemotherapy including rituximab (Mabthera)
followed by a biosimilar (Rixathon) as rst-line or salvage therapy. Data
were extracted from the electronic patient record, anonymized and evalu-
ated including response to treatment, progression-free survival (PFS) and
overall survival (OS).
Results: In 211 pts. (median age 69 years) the most common histological
subgroups was diuse large B-cell lymphoma (DLBCL) (38.4%), follicu-
lar lymphoma (FL) (26.5%), marginal zone lymphoma (11,8%) and other
subtypes (23,2%).171 pts. received a rst-line therapy, 1355 anti-CD20
antibody doses were applied during induction treatment (n=1051) and
maintenance (n=304). Anti-CD20 treatment consisted of 48.2% Mabthera,
34.8% Rixathon, 9.2% Mabthera s.c. 7.8% Obinutuzumab. A switch was
done in 51 rst-line treatments (24 DLBCL, 12 FL ,15 other subtypes).
Response to induction treatment was similar in switch and non-switch
groups in all histologic subtypes. Median PFS and OS was not reached
at a median follow up of 23 months and was comparable among switch
and non-switch groups. Similarly, in pts. receiving second-line treatment
(n=43) (switch in 7 pts.) no dierences in overall response, PFS and OS
occured (median follow up 26 months).
Discussion: e results suggest that a switch of Mabthera to the biosimi-
lar Rixathon has no impact on the eectiveness and outcome in dierent
subgroups of B-NHL.
Conclusion: A switch of Mabthera to the biosimilar Rixathon leads to
comparable outcomes and can be done safely in clinical routine.
Disclosure Statement: e authors declare no conict of interest.
679
Clinical characteristics and outcome of patients with relapsed
DLBCL undergoing autologous SCT, allogeneic SCT and CAR-T
cell therapy
Amelie Isabel Hartmann; Natalie Schub; Marianne Helweg;
Christiane Pott; Claudia Baldus
Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik für Innere Medizin
II mit den Schwerpunkten Hämatologie und Onkologie, Kiel, Deutschland
Background: Patients (pts) with diuse large B-cell lymphoma (DLBCL)
at rst chemo-sensitive relapse receive high-dose chemotherapy followed
by autologous stem cell transplantation (ASCT). At 2nd relapse, allogeneic
SCT (alloSCT) or CAR-T cell therapy (CART) have a curative potential.
Methods: is is a retrospective analysis of 126 pts with DLBCL who
underwent ASCT in rst (n=69) or 2nd relapse (n=16), alloSCT (n=23) or
CART (n=18) in 2nd relapse at UKSH Kiel from 2004 to April 2021
Result: Median age was 61 years in CART pts, 50 y in alloSCT and 61 y
in ASCT pts at 2nd relapse. CART pts presented with higher ECOG score
(28% ECOG 2-3) compared to alloSCT and ASCT pts (4% and 25%,
respectively) and higher HCT-CI score (2,44) (1,3 and 2,2 respectively).
Response to salvage treatment (complete or partial remission) was less
frequently achieved prior to CART (39%) than to alloSCT (70%) and
ASCT at 2nd relapse (44%). 56% of CART pts had chemorefractory disease,
while this was the case in only 22% alloSCT and 44% ASCT pts. Median
number of prior treatments was 2,5 for CART, 3 for alloSCT, and 3,25 for
ASCT pts. Response to treatment at 3 months was 50% aer CART, 65%
aer alloSCT and only 25% aer ASCT in 2nd relapse. At 6 months, 22% of
CART pts were still in remission compared to 35% aer alloSCT and 25%
aer ASCT. Early death during the rst 6 months aer treatment occurred
most frequently aer ASCT in 2nd relapse (38%) with 5 pts succumbing to
progressive disease (PD) and 1 due to an unrelated cause. 6% of CART pts
and 13% aer alloSCT died from PD and further 6% of CART pts and 13%
aer alloSCT from treatment related cause.
Discussion: Patients receiving CART were older and in worse condition
than those receiving ASCT or alloSCT. ASCT at 2nd relapse does not suf-
ciently control aggressive DLBCL leading to early death. AlloSCT is an
eective but toxic approach for a selected patient population.
Conclusion: CAR-T cell therapy at 2nd relapse is a useful treatment option
also for patients not qualifying for a more intensive treatment but patient
selection criteria need to be dened to improve long-term outcome.
Disclosure Statement: e authors declare no conict of interest.
691
A meta-analysis of ecacy of pomalidomide-based regimens
for the treatment of relapsed or refractory multiple myeloma
(RRMM) after lenalidomide (LEN) exposure
Katja Weisel1; Faith E. Davies2; Xavier Leleu3; Prisca Vogel4;
Sujith Dhanasiri5; Pauline Le Nouveau6
1University Medical Center Hamburg-Eppendorf, Hamburg, Deutschland
2New York University Grossman School of Medicine, Clinical Myeloma Program
Perlmutter Cancer Center, New York, USA
3Service dHématologie et Thérapie Cellulaire, Hôpital La Milétrie, Poitiers,
Frankreich
4Celgene, a Bristol Myers Squibb Company, Boudry, Schweiz
5Bristol Myers Squibb, Princeton, USA
6Amaris Consulting, Levallois-Perret, Frankreich
Background: Pomalidomide (POM)-based combination(s) are a standard
therapy for patients (pts) with RRMM previously treated with LEN. e
aim of this work was to provide a meta-analysis of progression-free sur-
vival (PFS) outcomes reported for POM-based combinations and generate
a pooled ecacy estimate.
Methods: A targeted literature search was performed to identify studies
conducted 2016–2020 in pts with RRMM previously treated with LEN.
Studies included in the meta-analysis enrolled pts who were treated
with POM plus dexamethasone (Pd) in combination with a proteasome
inhibitor (bortezomib [PVd], carlzomib [KPd], or ixazomib [IxaPd]),
monoclonal antibody (elotuzumab [EloPd], daratumumab [DPd], or
isatuximab [IsaPd]), or an alkylating agent (cyclophosphamide [PCd]).
Published Kaplan–Meier curves were digitized to reconstruct individual
patient data (IPD) through the Guyot algorithm. Reconstructed IPD were
used to conduct 3 unadjusted meta-analyses that generated the median
PFS for 3 groups: pts from studies with second-line (2L) treatment only,
pts from studies that included 2L pts (2L+), and all pts from all studies.
Result: Six randomized controlled trials (OPTIMISMM – PVd vs Vd,
APOLLO – DPd vs Pd, EMN-011 – KPd, ELOQUENT-3 – EloPd vs
Pd, ICARIA-MM – IsaPd vs Pd, NCT01432600 – PCd vs Pd) and 6 sin-
gle-arm trials (MM-014 – DPd, MMRC – KPd, NCT02185820 – KPd,
NCT02119468 – IxaPd, NCT02176213 – PCd, IFM2013 – PCd) were
identied. Median PFS was 21.3 months for 2L only pts, 16.9 months for
2L+ pts, and 14.1 months for all pts.
Discussion: POM-based combinations are an eective treatment strategy
in pts with RRMM previously treated with LEN. is analysis found that
POM-based regimens were more eective in pts in early-line treatment
(2L) compared with the overall population. POM delivers consistent e-
cacy and synergy in combination with proteasome inhibitors and mono-
clonal antibodies.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts172
Conclusion: ese data suggest that class switch is not always necessary
when making treatment decisions for pts with RRMM.
Reference:
Davies FE, et al. HemaSphere 2021;5:e478–479. EP1013.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
709
Idecabtagene vicleucel (ide-cel; bb2121); a BCMA-directed
CAR T cell therapy; for the treatment of patients with relapsed
and refractory multiple myeloma (RRMM): updated results
from KarMMa
Hermann Einsele1; Larry D. Anderson Jr2; Nina Shah3; Sundar Jagannath4;
Jesús Berdeja5; Sagar Lonial6; Noopur Raje7; David S. Siegel8;
Yi Lin9; Philippe Moreau10; Ibrahim Yakoub-Agha11; Michel Delforge12;
Hartmut Goldschmidt13; Katja Weisel14; Michele Cavo15; Donna Reece16;
Alessandro Rambaldi17; Anna Truppel-Hartmann18; Payal Patel19;
Liping Huang19; Timothy B. Campbell19; Kristen Hege19; Jesús San-Miguel20;
Nikhil C. Munshi21; Albert Oriol22
1University Hospital Würzburg, Würzburg, Deutschland
2Simmons Comprehensive Cancer Center, UT Southwestern Medical Center,
Dallas, USA
3University of California San Francisco, San Francisco, USA
4Mount Sinai Hospital, New York, USA
5Sarah Cannon Research Institute and Tennessee Oncology, Nashville, USA
6Emory School of Medicine, Atlanta, USA
7Massachusetts General Hospital, Boston, USA
8Hackensack University Medical Center, Hackensack, USA
9Mayo Clinic, Rochester, USA
10Centre Hospitalier Universitaire de Nantes, Nantes, Frankreich
11CHU de Lille, Univ Lille, INSERM U1286, Innite, Lille, Frankreich
12University Hospital Leuven, Leuven, Belgien
13University Hospital Heidelberg, Heidelberg, Deutschland
14University Medical Center of Hamburg-Eppendorf, Hamburg, Deutschland
15Bologna University School of Medicine, Bologna, Italien
16Princess Margaret Cancer Centre, Toronto, Kanada
17University of Milan and ASST Papa Giovanni XXII, Bergamo, Italien
18bluebird bio, Cambridge, USA
19Bristol Myers Squibb, Princeton, USA
20Clínica Universidad de Navarra, CIMA, CIBERONC, IDISNA, Pamplona, Spanien
21The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Multiple
Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston,
USA
22Institut Josep Carreras and Institut Català dOncologia, Hospital Germans Trias i
Pujol, Badalona, Spanien
Background: Patients (pts) with RRMM previously treated with immuno-
modulatory agents (IMiDs), proteasome inhibitors (PIs), and anti-CD38
monoclonal antibodies (mAbs) have poor outcomes with subsequent
therapy (tx). Ide-cel, a BCMA-directed CAR T cell tx, showed frequent,
deep, and durable responses in heavily pretreated pts with RRMM in the
pivotal KarMMa study (NCT03361748; Munshi NC et al. N Engl J Med
2021). We report updated results from this trial.
Methods: Pts had ≥ 3 prior regimens (including IMiD, PI, and anti-CD38
mAb) and disease refractory to last tx per IMWG criteria. Aer 3 days of
lymphodepletion, pts received 150–450 × 106 CAR+ T cells (target dose
levels). Endpoints included overall response rate (ORR; primary), com-
plete response (CR) rate (key secondary), progression-free survival (PFS),
overall survival (OS), and safety.
Result: Of 140 enrolled pts, 128 received ide-cel. Among treated pts,
median age was 61 y. Pts had a median of 6 prior tx, with 84% being
triple-class refractory and 26% penta-refractory (2 IMiDs, 2 PIs, and 1
anti-CD38 mAb). Most pts (88%) had bridging therapy. At data cuto
(Dec 21, 2020), median follow-up for surviving pts was 24.8 mo. ORR was
73% (CR rate, 33%); median PFS was 8.6 mo. In pts with ≥ CR, median
PFS was 22.4 mo. Outcomes improved at higher doses, with ORR of 81%,
CR rate of 39%, and median PFS of 12.2 mo at 450 × 106 CAR+ T cells.
Median OS in all treated pts was 24.8 mo; the 24-mo OS rate was 51%.
Most common any-grade toxicities were neutropenia (91%) and cytokine
release syndrome (CRS; 84%). CRS was mostly grade 1/2; 5 pts (4%) had
grade 3; 1 pt each (< 1%) had grade 4 and 5 events. Investigator-identied
neurotoxicity occurred in 23 pts (18%); 5 (4%) had grade 3 and 0 had
grade ≥ 4 events.
Discussion: Updated results from KarMMa continue to demonstrate
durable and deep responses with ide-cel in triple-class–exposed pts with
RRMM.
Conclusion: Ecacy and safety data reect prior reports and support a
favorable clinical benet–risk prole for ide-cel across target dose levels.
Prior presentation
IMW 2021. Abstract OAB27.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
957
Accuracy and Reliability of German Websites for Information
on Monoclonal Gammopathy of Undetermined Signicance
Emma Kreutzer1; Henrike Staemmler1; Sandra Sauer2; Katharina
Kriegsmann2
1Universitätsklinikum Heidelberg - Medizinische Fakultät, Heidelberg,
Deutschland
2Universitätsklinikum Heidelberg, Heidelberg, Deutschland
Background: Monoclonal gammopathy of undetermined signicance
(MGUS) is a clonal, premalignant plasma cell or B-cell disorder. MGUS
patients oen seek disease-related information online. However, the qual-
ity of online resources available for MGUS is questionable.
Methods: e quality of 900 German websites from Google, Bing, and
Yahoo was evaluated.
Result: e websites did not dier regarding their search rank or between
the search engines. e 83 unique websites showed a medium to poor
general quality (median JAMA score 3 of maximum 4 points, only 4%
websites with a valid HON certicate). e patient- (user-) focused qual-
ity was poor (median sum DISCERN score 24 of maximum 80 points).
e reading level was very dicult (29 of maximum 100 points according
to the Flesch Reading Ease score). e content level was very low (11 of
maximum 50 points). 23% of websites contained misleading/wrong facts.
Websites provided by scientic/governmental organizations had a higher
content level compared to websites provided by foundation/advocacy or
news/media.
Discussion: Similar previously published analyses oen focus on oto-
rhinolaryngology-related topics, idiopathic pulmonary brosis, SARS-
CoV-2 or neurological disorders. Precancerous conditions and cancer
entities were rarely in the focus of such evaluations. is study was per-
formed in a reproducible and objective score-based manner, applying a set
of well-established scores covering the aspects of general, patient- (user-)
focused quality, and MGUS-related content.
Conclusion: MGUS-relevant online sources showed low general and
patient-focused quality and poor content. Information is provided on a
high reading level. Incorporation of quality indices and regular review of
content is warranted.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 173
971
ELOQUENT-3 Trial: Elotuzumab Plus Pomalidomide and
Dexamethasone for Relapsed/Refractory Multiple Myeloma -
Final Overall Survival Analysis
Marc-Steen Raab1; Meletios Dimopoulos2; Dominik Dytfeld3; Sebastian
Grosicki4; Philippe Moreau5; Naoki Takezako6; Mitsuo Hori7; Xavier Leleu8;
Richard Leblanc9; Kenshi Suzuki10; Paul G Richardson11; Mihaela Popa
Mckiver12; Ying-Ming Jou12; David Yao12; Prianka Das12; Jesús San-Miguel13
1Heidelberg University Hospital, Department of Medicine V, Heidelberg,
Deutschland
2National and Kapodistrian University of Athens School of Medicine, Athens,
Griechenland
3Karol Marcinkowski University of Medical Sciences, Department of Hematology
and Bone Marrow Transplantation, Poznań, Polen
4Silesian Medical University, Katowice, Polen
5University Hospital, Nantes, Frankreich
6National Hospital Organization Disaster Medical Center, Department of
Hematology, Tokyo, Japan
7Ibaraki Prefectural Central Hospital, Department of Hematology, Kasama, Japan
8Centre Hospitalier Universitaire de PoitiersLa Milétrie, Poitiers, Frankreich
9University of Montreal, Hôpital Maisonneuve-Rosemont, Montreal, Kanada
10Japanese Red Cross Medical Center, Department of Hematology, Tokyo, Japan
11DanaFarber Cancer Institute, Jerome Lipper Multiple Myeloma Center,
Boston, USA
12Bristol Myers Squibb, Princeton, USA
13Clínica Universidad de Navarra (CUUN), Centro de Investigación Médica
Aplicada, Instituto de Investigación Sanitaria de Navarra (IDISNA), Centro de
Investigación Biomédica en Red de Cáncer (CIBERONC), Pamplona, Spanien
Background: In the randomized phase 2 ELOQUENT-3 trial
(NCT02654132), elotuzumab combined with pomalidomide/dexameth-
asone (EPd) signicantly improved progression-free survival (PFS) ver-
sus pomalidomide/dexamethasone (Pd) in patients (pts) with relapsed/
refractory multiple myeloma (RRMM). A preliminary analysis of overall
survival (OS) (minimum follow-up of 9.1 months [mo]) showed a trend
favoring EPd over Pd (hazard ratio [HR] 0.62; 95% CI, 0.30–1.28). Here
we present nal OS results.
Methods: Pts with RRMM who had received ≥ 2 prior lines of therapy,
disease refractory to last therapy, and either refractory or relapsed and
refractory to lenalidomide and a proteasome inhibitor (PI), were random-
ized (1:1) to receive EPd or Pd. e primary endpoint was PFS per inves-
tigator assessment. OS was a secondary endpoint planned to be tested
hierarchically. Final OS analysis was pre-specied to occur aer 78 deaths
and was also analyzed within pt subgroups.
Result: A total of 117 pts were randomized to EPd (n = 60) and Pd (n
= 57). At the January 11, 2021 data cuto (minimum follow-up of 45
mo), among treated pts (EPd, 60; Pd, 55), there were 37 (61.7%) deaths
in the EPd group and 41 (74.5%) in the Pd group, most commonly due
to disease progression (EPd 41.7%, Pd 49.1%). Median (95% CI) OS was
signicantly improved with EPd (29.8 [22.9–45.7] mo) versus Pd (17.4
[13.8–27.7] mo), with a HR of 0.59 (95% CI, 0.37–0.93; P = 0.0217). EPd
improved OS in most pt subgroups. e safety prole of EPd was consis-
tent with prior reports, with no new safety signals detected.
Discussion: EPd demonstrated a statistically signicant and clinically
meaningful improvement in OS versus Pd in pts with RRMM previously
treated with lenalidomide and a PI who had disease refractory to last
therapy.
Conclusion: In this setting, ELOQUENT-3 is the rst randomized study
of a triplet regimen incorporating a monoclonal antibody and Pd that
improved both PFS and OS signicantly.
ese data were presented previously (Dimopoulos MA, et al. 18th
International Myeloma Workshop; September 8–11, 2021; Vienna,
Austria. Poster P-193).
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
991
Exploring Alternative Dosing Regimens of Single-Agent
Belantamab Mafodotin on Safety and Ecacy in Patients
With Relapsed or Refractory Multiple Myeloma (RRMM):
DREAMM-14
Hans Salwender1; Malin Hultcrantz2; Dave Kleinman3;
Pavandeep Ghataorhe4; Astrid Mckeown4; Wei He4; Thomas Ling4;
Roxanne Jewell4; Julie Byrne4; Laurie Eliason4; Emma Scott4;
Joanna Opalinska4
1Askepios Tumorzentrum Hamburg, AK Altona and St. Georg, Hamburg,
Germany
2Memorial Sloan Kettering Cancer Center, New York, USA
3University of Rochester, New York, USA
4GlaxoSmithKline, London, Vereinigtes Köngreich
Background: Belantamab mafodotin (belamaf; BLENREP) is a rst-
in-class, monomethyl auristatin F containing, B-cell maturation anti-
gen-directed antibody-drug conjugate. DREAMM-14 (NCT05064358)
investigates whether an improved benet/risk prole of single-agent
belamaf can be achieved by modifying the dose, schedule, or both, relative
to the approved dosing regimen (2.5 mg/kg Q3W) to reduce ocular events
without clinically meaningful decrease in ecacy.
Methods: is Phase II, randomized, open-label study includes adults
with RRMM and ≥3 prior lines of therapy (LOT). Patients are random-
ized into Arms A–D (n=40 each) and Arm E (n=20) in parallel stratied
by the International Staging System (I vs II vs III) and prior LOT (3 vs ≥4).
Belamaf is administered as follows - Arm A: 2.5 mg/kg Q3W; Arm B: 1.9
mg/kg Q3W; Arm C: 2.5 mg/kg Q6W; Arm D: 1.9 mg/kg Q6W; Arm E:
1.9 mg/kg Q6W. Dose modications are based on oncology sta assess-
ment of ocular symptoms and visual acuity.Corneal ndingsare assessed
by eye care professionals (ECP).
Result: Patients in all Arms have response assessments, safety assess-
ments, and ophthalmic exams performed by ECP Q3W regardless of dos-
ing schedule. Ocular event-related dose modications (except in Arm E)
are guided by a modied Keratopathy and Visual Acuity scale.
Discussion: e primary endpoint is incidence of ocular events. Key sec-
ondary endpoints are ocular safety/tolerability, overall safety/tolerability,
pharmacokinetics, and ecacy outcomes. Follow-up for progression-free
survival is Q3W until progressive disease, start of new anticancer therapy,
withdrawal of consent, end of study, or death.
Conclusion: First patient rst visit was 04Mar22.
Funding: GSK (Study 209628); drug linker technology licensed from
Seagen Inc.; mAb produced using POTELLIGENT Technology licensed
from BioWa. Presented as TPS8073 at ASCO, Jun 3-7, 2022; submitted
with permission from the original authors. ©2022 American Society of
Clinical Oncology, Inc. Reused with permission. All rights reserved.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts174
MIC/Robotic
Poster
813
Stereotactic percutaneous electrochemotherapy as primary
approach for unresectable large HCC at the hepatic hilum
Lukas Luerken1; Ingo Einspieler1; Wibke Uller2; Christian Stroszczynski1
1Universitätsklinikum Regensburg, Radiologie, Interventionelle Onkologie,
Regensburg, Deutschland
2Universitätsklinikum Freiburg, Radiologie, Interventionelle Radiologie, Freiburg
im Breisgau, Deutschland
Background: Electrochemotherapy (ECT) is a non-thermal ablative tech-
nique that combines chemotherapy and the application of electric pulses
for reversible cell membrane electroporation. is method was recently
performed in the treatment of deep-seated liver tumors during open sur-
gery but experience about percutaneous ECT is rare and further develop-
ments like combination of percutaneous ECT with stereotactic navigated
devices may be very promising.
Methods: A 75-years old male patient with Child A liver cirrhosis pre-
sented with a 4.7 cm large central, unresectable HCC involving liver seg-
ments IV/VIII and a satellite HCC with 1.3 cm in segment V. e portal
vein showed thrombosis resulting in cavernous transformation while the
hepatic artery and the central bile ducts were located in close proximity to
the HCC. Stereotactic ECT of the central HCC and MWA of the satellite
was performed in one session under general anaesthesia.
Result: Magnetic resonance imaging (MRI) performed 24h aer the pro-
cedure conrmed complete devascularization of tumor and satellite. e
patient was discharged two days aer the procedure without complica-
tions. Contrast-enhanced MRI 6 weeks and 6 months aer ECT showed
complete response with no residual or recurrent HCC and without any
signs of damage of the central bile ducts or aection of the liver artery.
Discussion: e primary tumour was unresectable and not suited for
thermic ablation techniques such as RFA and MWA because of the close
proximity to the major blood vessels and bile ducts and was too large for
IRE. e possibility to navigate the percutaneous transhepatic approach
in accordance to the individual anatomy using a stereotactic navigation
system may be technically superior to ECT during open surgery or percu-
taneous techniques using uoroscopy.
Conclusion: Stereotactic percutaneous ECT has the potential to be used
as a treatment method for HCC with diameters of more than 4cm, even in
close proximity to critical structures like major blood vessels and central
bile ducts.
Disclosure Statement: e authors declare no conict of interest.
Molecular Pathology
Poster
181
Opportunities and Limitations - Use of Idylla assays in various
tumor samples in routine diagnostic settings
Sanga Mitra Boppudi1; Stefanie Scheil-Bertram1; Elisabeth Faust1;
Annette Fisseler-Eckho1,2
1Institute of Pathology and cytology, Helios Dr. Horst Schmidt Kliniken
Wiesbaden, Wiesbaden, Deutschland
2Gemeinschaftspraxis für Pathologie, Wiesbaden, Deutschland
Background: For cancer patients’ treatment, diagnostics concerning
tumor type and determination of molecular markers in short turnaround
time is very critical. e Biocartis-Idylla molecular assays are well estab-
lished in many laboratories for qualitative detection, short turnaround
time and routine screening of clinically relevant oncogenic mutations.
According to the manufacturer, all IVD-assays are recommended to use
only with FFPE tissue samples of 5-10µM dissections with at least 10%
tumor content.
Methods: In this current study, the dierent source materials used as input
material in the assay cartridges are (1) gDNA isolated from FFPE tissues,
cryomaterial, frozen tissue cuts, and HE stained slides. (2) tissue scratched
from normal 5µM and 2µM FFPE sections (3) tissue scratched from HE
slides (4) direct input of cryomaterial uid (5) direct input of tissue sec-
tion uid. Along with dierent input materials, the study also included
archival FFPE tissue sections dating from 15 years back. To check their
performance, all the IVD-Idylla assays catridges were also tested for dif-
ferent pan-tumor samples individually.
Results: All the assays tested with tissue scratched from FFPE/HE sec-
tions showed above 96% of accuracy, sensitivity, and specicity individ-
ually. is study indicates that minimum of 8ng/µl gDNA concentration
is required with at least 10µl input (80ng) for certainty of results. For use
of uids, a direct input of 20µl is recommended for better performance.
e Idylla assays also performed exceptionally well on the archival tissues
showing above 94% eciency. e use of IVD-labeled assays for other
solid tumors was also remarkable with more than 95% sensitivity and
specicity.
Discussion: e performance test and accuracy of Idylla assays with dif-
ferent tissue/source materials along with the recommended FFPE material
showed high eciency with certain limitations.
Conclusions: For use of Idylla assays, both qualitative and quantitative
applicability of dierent tumor materials could produce ecient results in
dierent diagnostic settings.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 175
381
Ki-67 gene expression
Sigrid Uxa; Paola Castillo-Binder; Robin Kohler; Konstanze Stangner;
GerdMüller; Kurt Engeland
Medizinische Fakultät, Universität Leipzig, Molekulare Onkologie, Leipzig,
Deutschland
Background: Ki-67 serves as a prominent cancer marker.
Results: We describe how expression of the MKI67 gene coding for Ki-67
is controlled during the cell cycle. MKI67 mRNA and Ki-67 protein are
maximally expressed in G2 phase and mitosis. Expression is dependent on
two CHR elements and one CDE site in the MKI67 promoter. DREAM
transcriptional repressor complexes bind to both CHR sites and down-
regulate expression in G0/G1 cells. Upregulation of MKI67 transcription
coincides with binding of B-MYB-MuvB and FOXM1-MuvB complexes
from S phase into G2/M. Importantly, binding of B-MYB to the two CHR
elements correlates with loss of CHR-dependent MKI67 promoter activa-
tion in B-MYB knockdown experiments. In knockout cell models, we nd
that DREAM/MuvB-dependent transcriptional control cooperates with
the RB Retinoblastoma tumor suppressor. Furthermore, the p53 tumor
suppressor indirectly downregulates transcription of the MKI67 gene.
is repression by p53 requires p21/CDKN1A.
Discussion: ese results are consistent with a model in which DREAM,
B-MYB-MuvB, and FOXM1-MuvB together with RB cooperate in cell
cycle-dependent transcription and in transcriptional repression following
p53 activation.
Conclusion: We present mechanisms how MKI67 gene expression fol-
lowed by Ki-67 protein synthesis is controlled during the cell cycle and
upon induction of DNA damage as well as upon p53 activation.
(Uxa et al. Cell Death and Dierentiation, 2021; in press)
Disclosure Statement: e authors declare no conict of interest.
554
Frequency of KRAS G12C plus co-mutations in solid tumors
and adequate test methods
Stefanie Schatz; Markus Falk; Markus Tiemann
Institut für Hämatopathologie Hamburg, Hamburg, Deutschland
Purpose: KRAS mutations were identied decades ago as oncogenic driv-
ers in various tumor entities. KRAS mutation analysis has recently gained
relevance since KRAS G12C specic and KRAS agnostic inhibitors have
nally entered clinical trials. For several years, many diagnostic institu-
tions have already routinely tested solid tumors for the presence of KRAS
mutations using various methods. ese data may prove important in
understanding the distribution of targetable KRAS alterations throughout
dierent tumor entities.
Methods: KRAS mutation status of solid tumor biopsies from patients
with advanced disease was collected retrospectively as assessed by hybrid
capture multi gene next generation sequencing (HC-NGS). Samples were
requested for routine driver mutation analysis between 2016 and 2021 and
data was retrospectively collected from our internal diagnostic documen-
tation soware.
Results: e majority of 2923 solid tumors were lung cancer biopsies,
but in addition colorectal-, mamma-, pancreatic carcinoma and oth-
ers. In 24.9% of tumor samples KRAS mutations aected codon G12X,
1.9% codon Q61X, A146X 0.1%, in 0.8% of samples other codons were
mutated. KRAS codon G12C has gained particular attention since the
advent of clinical trials investigating the ecacy of G12C specic KRAS
inhibitors. Among the >600 tumors harboring a G12X mutation, G12C
constituted the most prevalent amino acid exchange (47.0%), followed by
G12V (22.2%), G12D (16.3%), G12A (9.3%), G12S (2.0%), G12F/R (1.4%)
and G12L/E with each 0.2%.
Discussion: KRAS mutations, especially G12C is a common driver in
human cancers. Clinically relevant co-mutations like TP53, KEAP, STK11
and POLE have been discussed to inuence outcome and may gain impor-
tance in the future for molecular therapy stratication.
Conclusions: Although KRAS mutations are diagnostically assessible by
conventional test methods, we propose HC-NGS as a reasonable assay
to additionally detect co-mutations and potential resistance alterations
simultaneously in one assay.
Disclosure Statement: e authors declare the following: M. Tiemann:
Astra Zeneca Boehringer Ingelheim BMS MSD Novartis Roche Takeda
787
A Lesson from Lynch Syndrome: Five-Year Survival
of a Patient with Metastatic Pancreatic Cancer,
Post Ovarian and Breast Cancer and MLH1 Heterozygosity
Nurlan Abdullayev1; Jürgen Weitz2; Florian Lordick3; Thomas Brunner1
1Universtiätsmedizin Magdeburg, Klinik für Strahlentherapie, Magdeburg,
Deutschland
2Universitätsklilnikum Dresden, Klinik für Chirurgie, Dresden, Deutschland
3Universitätsklinikum Leipzig, Klinik für Hämatoonkologie, Leipzig, Deutschland
Aim: A patient with atypical Lynch syndrome (LS) and progressive pan-
creatic cancer (PDAC) surviving >5 yrs aer cured ovarian and breast
cancer posing a substantial therapeutic dilemma with lately evolving lung
mets and limited chemo tolerance.
Methods: e case is put into context of LS with MLH1 heterozygosity
and microsatellite stability (MSS).
Results: History: ovarian cancer @ 37 (resection, relapse aer 3 yrs, surgi-
cal salvage + adjuvant CDDP chemoRT), breast cancer @ 62 (BET: pT1c
pN0 G1 ER+/PR+;adj. RT and anastrozol), and PDAC @ 67 yrs with a
positive family history but stable microsatellites.PDAC was resected in
03/2016 (pT3 pN1(3/23) V1 L1 Pn1; K-Ras mt) plus adj. poorly tolerated
GEM. Local recurrence in 6/18 was treated by SBRT (12 x 5.5 Gy). A sin-
gular brain met was resected in 8/18 + adj. RT. SBRT of a single lung met
in 10/18. Multiple lung mets in 1/19 <= 6 mm, progressed by 3/19.From
4-8/19, 8 x FOLFIRINOX, cCR in 12/19. Local relapse of brain metin
03/20, re-SFRT with 7 x 5 Gy. Recurrent lung mets and FOLFOXnalIRI.
Last contact 08/21, stable performance status.
Conclusion: Patients with a pathogenic variant of MLH1 have a risk to
develop colorectal cancer (22%-53%), endometrial cancer (14-54%) and
other cancers e.g. ovarian (4%-20%), breast (5%-18%), pancreas (0.4%-
40%). Our patient had atypical LS with MLH1 heterozygosity but MSS.
erefore, immune checkpoint inhibitor therapy was not recommended
and the patient had excellent response to chemotherapy and radiotherapy.
However, salvage options for the patient are required. FOLFIRINOX rein-
duction was chosen. Alternatively, SBRT plus 1-2 courses of FOLFIRINOX
followed by ICI therapy would be an option; based on RT-induced sen-
sitization to ICI and increased mutation frequency aer RT of MSH1
decient tumour cells (Yan T et al. CCR 2009) as well as 5-FU / oxalipla-
tin-induced ICI sensitization (van der Kraak J Immunother Cancer 2016;
Kalanxhi E et al. Cancers 2020).
Disclosure Statement: e authors declare no conict of interest.
902
Evaluation of the AVENIO Tumor Tissue Comprehensive
Genomic Proling (CGP) Kit
Kay Hertel1; James Oughton2; Ulrich Schlecht3; Ina Vogl4;
Thomas Wieland4; Carlo Messina5
1Helios MVZ Pathologie, Erfurt, Deutschland
2Foundation Medicine, Inc., Cambridge, USA
3Signature Diagnostics GmbH, Potsdam, Deutschland
4Foundation Medicine GmbH, Penzberg, Deutschland
5Roche Diagnostics Solutions, Inc., Basel, Schweiz
Background: AVENIO Tumor Tissue CGP (AVENIO Kit) is a manual,
distributable, and research-use-only kit. It covers the same genomic
regions, 324 genes, as the FDA-approved FoundationOne CDx assay
(F1CDx). We wished to determine the agreement of both assays given the
dierent chemistry and bioinformatics pipelines.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts176
Methods: Aliquots of the same DNA extraction of 50 formalin-xed par-
an-embedded solid tumour tissue samples (majority breast [n = 15],
colon [n = 13] and prostate [n = 12]) served as input for both assays. e
AVENIO Kit was performed at Signature Diagnostics GmbH (Potsdam,
Germany) and F1CDx at Foundation Medicine GmbH (Penzberg,
Germany). Overall percent agreement (OPA), weighted kappa (WK), and
95% condence intervals (95% CI) were calculated.
Result: e AVENIO Kit had a median coverage of 1870X (460X with
F1CDx). In both assays, a median of 9.5 short variants per sample (range:
3–291; restricted to one exon: single/multiple nucleotide variants, inser-
tions, and deletions) were detected. OPA of short variants between assays
was 99.75% (95% CI: 99.71–99.79) and OPA of complex variants (crossing
exon borders: deletions, truncations, fusions, and rearrangements) was
99.41% (98.92–99.72). OPA of copy number alterations between assays
was 98.32% (95% CI: 97.97–98.63). WK of tumor mutational burden
(TMB) classications was 0.88 (95% CI: 0.78–0.98). Microsatellite stabil-
ity status was identical between assays in 45 samples; two were microsat-
ellite instability (MSI)-high and ve could not be evaluated by F1CDx.
WK of genome-wide loss of heterozygosity (gLOH) status was 0.82 (two
gLOH-high; 95% CI: 0.62–1.00).
Discussion: e higher coverage of the AVENIO Kit is a result of the
molecular, bioinformatics pipeline and the dierent chemistry. Agreement
decreases with the complexity of variations.
Conclusion: We observed a high degree of agreement between the
AVENIO Kit and F1CDx for all genomic variants and the genomic signa-
tures TMB, MSI, and gLOH.
Pres. at EFLM 2022
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
Molecular Therapeutics
Poster
555
The University of Munich Virtual Molecular Tumorboard -
Patient Centered Care Meets Future Needs
Katharina Rühlmann1; Madeleine Flach1; Dorottya Biro1;
KathrinHeinrich2,3; Frank Ziemann2,3; Tobias Herold2,3; Louisa
vonBaumgarten4; Philipp Greif2,3; Irmela Jeremias3,5,6; Rachel Würstlein7;
Andreas Jung3,8; Jörg Kumbrink3,8; Thomas Kirchner3,8;
FrederickKlauschen3,8; Volker Heinemann1,2,3; Benedikt Westphalen1,2,3;
Korbinian Hasselmann2
1LMU University Hospital Munich, Comprehensive Cancer Center (CCC Munich
LMU), München, Deutschland
2LMU University Hospital Munich, Department of Medicine III, München,
Deutschland
3German Cancer Consortium (DKTK), Partner Site Munich, Deutschland
4LMU University Hospital Munich, Department of Neurology, München,
Deutschland
5Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital,
Department of Pediatrics, München, Deutschland
6Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit
und Umwelt (GmbH), Department of Apoptosis in Hematopoietic Stem Cells,
München, Deutschland
7LMU University Hospital Munich, Gynecologic Oncology Center, Breast Center
and Comprehensive Cancer Center Munich, Department of Obstetrics and
Gynecology, München, Deutschland
8LMU University Hospital Munich, Institute of Pathology, München, Deutschland
Background: Molecular Tumorboards (MTB) are important clinical
platforms in precision oncology. e MTB of the Comprehensive Cancer
Center at University of Munich was implemented in 2016 to discuss treat-
ment concepts based on molecular tumor proling. To provide broader
access to the University of Munich MTB, especially for Externals (eg.
community hospitals, local medical centers and practices) and readjusting
to the SARS-CoV2 pandemic, we transitioned from face-to face MTB to a
virtual setting (vMTB) in early 2020. e vMTB allows building loco-re-
gional expert networks for exchange on clinical studies and education and
helps to capture real world data across healthcare systems.
Methods: e vMTB takes place on a web-based platform. For security
purposes, the platform runs on in-house servers. However, we provide
a secure option to grant access rights to external users. e internal data
privacy guidelines, like anonymous case presentations and personalized
logins are adhered to.
Result: In 2020, 609 patients were discussed in the vMTB. Compared
with 2019 and despite the pandemic situation the clinical case number
increased by a factor of 1.5. Due to this rapid growth, the rhythm of
the vMTB changed on a weekly basis. 90/609 patients were enrolled by
Externals; this represents an increase from 6% to 15% of all patient regis-
trations compared with 2019. At present, the precision oncology program
cooperates with eleven partner sites mainly in southern Bavaria.
Discussion/Conclusion: e concept of virtualization removes geo-
graphical barriers, facilitates communication and opens the opportunity
to grow as an interdisciplinary network while simultaneously allowing
external patients to remain in their familiar treatment environment. e
vMTB helps closing the gap between healthcare sectors and allows an easy
access of internal and external partners to this innovative clinical struc-
ture. is holistic and patient-centered approach allows to further imple-
mentation of precision oncology into clinical practice.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
785
Whole Exome Sequencing to Select Targeted Therapies
forPatients with Breast or Gynecologic Cancer supported
byan Online Decision-Making Platform
Bernadette Jäger; Natalia Krawczyk; Dorothee Haas; Ellen Honisch;
Anne Kathrin Volkmer; Eugen Ruckhäberle; Dieter Niederacher;
Tanja Fehm
1Universitätklinikum Düsseldorf, Frauenklinik, Düsseldorf, Deutschland
Background: e aim of this proof-of-concept study was to select therapy
targets or dene potential therapy resistance and safety issues in patients
with advanced breast (BC) or gynecologic cancer (GC). e project was
supported by an online decision-making platform (MH guide®, Molecular
Health, Heidelberg) to simplify data interpretation for daily clinical
routine.
Methods: We established next generation sequencing (NGS) based whole
exome sequencing (WES) of patients with advanced BC (n=44) of any
subtype or GC (n=8). Patients with GC suered from ovarian n=2, vulva/
vaginal n=3, endometrial n=2 or cervical cancer n=1. WES was performed
from most recent tumor samples (metastatic lesions or primary tumors)
and corresponding blood samples (germline). e indication for study
participation and the discussion of the results took place in our molecular
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 177
tumor conference. Gene alterations (GA) were categorized in “eective,
“ineective” and “safety” according to MH guide® criteria.
Result: In BC patients, we detected 44 potentially eective GA (mutations)
in 19 dierent genes. Most GA were found in TP53 (n=7), PIK3CA (n=6)
and CDH1 (n=5). BRCA1 and BRCA2 were altered in 2 and 5 patients,
respectively. PARP- and PI3K- inhibitors were recommended accordingly.
High TMB and MSI were discovered in 6 and 15 patients. GC patients had
15 potentially eective GA in 12 dierent genes with CHEK2 and KRAS
mutated in two patients. “Ineective” and “safety” GA were analyzed as
well and will be reported in the same way.
Discussion: WES is technically feasible but selecting targeted therapies in
advanced BC and GC based on WES results is still challenging. Long time
intervals occur until results are reported and the procedure is cost-inten-
sive. In addition, for many of the “eective” gene alterations detected in
our collective there is still no approved treatment option.
Conclusion: Consequently, we established an in-house gene panel (ther-
apy-resistance-toxicity-panel (TRTP)) to quickly choose and validate tar-
geted therapies and optimize BC and GC treatment in future.
Disclosure Statement: e authors declare no conict of interest.
840
Tepotinib + getinib in patients with EGFR-mutant NSCLC
with MET amplication (METamp): nal analysis of INSIGHT
Chong Kim Liam1; Azura Rozila Ahmad2; Te-Chun Hsia3; Jianying Zhou4;
Dong-Wan Kim5; Ying Cheng6; Shun Lu7; Sang Won Shin8; James
Chih-Hsin Yang9; Yiping Zhang10; Jun Zhao11; Rolf Bruns12; Andreas
Johne13; Yi-Long Wu14
1University of Malaya, Faculty of Medicine, Kuala Lumpur, Malaysia
2Beacon Hospital, Selangor, Malaysia
3China Medical University Hospital, Taichung City, Taichung City, Taiwan
4The First Aliated Hospital, Zhejiang University, Hangzhou, China, VR
5Seoul National University Hospital, Seoul, Korea, Dem. People’s Rep. of
6Jilin Province Cancer Hospital, Changchun, China, VR
7Shanghai Chest Hospital, Shanghai, China, VR
8Korea University Anam Hospital, Seoul, Korea, Dem. Peoples Rep. of
9National Taiwan University Hospital, Taipei, Taiwan
10Zhejiang Cancer Hospital, Hangzhou, China, VR
11Beijing Cancer Hospital, Beijing, China, VR
12Department of Biostatistics, Merck Healthcare KGaA, Darmstadt, Deutschland
13Global Clinical Development, Merck Healthcare KGaA, Darmstadt,
Deutschland
14Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital
and Guangdong Academy of Medical Sciences, Guangzhou, China, VR
Background: In the INSIGHT trial primary analysis (NCT01982955;
median follow-up: 21.8 months), tepotinib (a potent, highly selective,
once daily [QD] MET inhibitor) + getinib improved ecacy vs chemo-
therapy (CT) in patients (pts) with EGFR-mutant (m) NSCLC and resis-
tance to anti-EGFR therapy due to METamp (Wu et al, Lancet Respir Med
2020). Here we report nal analyses from INSIGHT (data cut-o: Sept 3,
2021; median follow-up: 57.5 months).
Methods: Pts with EGFR-m (T790M-negative) NSCLC and anti-EGFR
resistance, with MET gene copy number (GCN) ≥5 and/or MET:CEP7
≥2 by FISH (METamp), and/or MET IHC 2+/3+ (MET overexpression),
were randomized to tepotinib 500 mg (450 mg active moiety) + getinib
250 mg QD or CT. Primary endpoint was progression-free survival (PFS)
per investigator. Preplanned analyses evaluated pts with METamp.
Result: In 19/55 randomized pts (34.5%) with METamp (GCN ≥5, n=18;
MET:CEP7 ≥2, n=13; MET IHC 3+, n=17), median age was 60.4 years,
68.4% were never-smokers, and prior EGFR inhibitors were getinib
(57.9%), afatinib (21.1%), erlotinib (10.5%), and icotinib (10.5%). Median
duration of tepotinib + getinib was 11.3 months (range: 1.1–56.5), with
treatment duration >1 year in 6 pts (31.6%) and >4 years in 3 pts (15.8%).
Two pts continued treatment outside the study. Tepotinib + getinib
(n=12) improved outcomes vs CT (n=7). Respectively, median PFS was
16.6 vs 4.2 months (HR=0.13; 90% CI: 0.04, 0.43), median overall survival
(OS) was 37.3 vs 13.1 months (HR=0.10; 0.02, 0.36), objective response
rate was 67% vs 43% (odds ratio=2.67; 0.37, 19.56), and median dura-
tion of response was 19.9 (7.0, not estimable [ne]) vs 2.8 months (2.8, ne).
Treatment-related Grade ≥3 AEs occurred in 7 pts (58.3%) with tepotinib
+ getinib and 5 (71.4%) with CT. In pts with MET IHC 3+ (n=34; includ-
ing 17 pts with METamp), tepotinib + getinib also improved PFS (HR
0.35; 90% CI: 0.17, 0.74) and OS (HR 0.44; 0.23, 0.84) vs CT.
Conclusion: Tepotinib + getinib improved PFS and OS vs CT in pts with
EGFR-m NSCLC with METamp. INSIGHT 2 is evaluating tepotinib +
osimertinib in this setting
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
929
Targeting BRD4 potentiates YB-1 dependent oncolytic
adenovirus XVir-N-31 through E1A12S-mediated redirection
of cellular transcription machinery to viral genomes
Florian G. Klein1; Felicia Segeth2; Klaus Mantwill1; Viktoria Bondarets1;
Marvin Thielert3; Matthias Mann3; Jürgen E. Gschwend1; Andreas Kolk2;
Roman Nawroth1; Per Sonne Holm2,4
1Klinikum Rechts der Isar, Technical University of Munich, Department of
Urology, Munich, Deutschland, 2Medical University of Innsbruck, Department
of Oral and Maxillofacial Surgery, Innsbruck, Österreich, 3Max Planck Institute of
Biochemistry, Proteomics and Signal Transduction, Martinsried, Deutschland,
4XVir Therapeutics GmbH, Munich, Deutschland
Background: e epigenetic reader protein BRD4 orchestrates eukaryotic
and adenoviral gene expression via the RNA-Polymerase II machinery.
XVir-N-31, a YB-1 dependent oncolytic adenovirus with a deletion of
the adenovirus E1A13S protein that binds to the eukaryotic cyclin-de-
pendent kinase 9 (CDK9), shows reduced transactivation activity and
consequently reduced replication and cancer cell killing capacity. In this
study, we evaluated the role of BRD4 in XVir-N-31 gene expression, viral
genome replication and subsequent tumor cell killing.
Methods: We investigated XVir-N-31 and targeting of BRD4 via inhibi-
tion, protein degradation, genetic depletion or acquired resistance in vitro
and in a nude mice model in vivo. Characterization of the underlying
molecular mechanism was performed by protein overexpression, viral
transactivation assays, Co-IP and ChIP immunogenic pull-down assays,
and LC-MS proteomics analysis.
Result: Inhibition of BRD4 by the small molecule JQ1 unexpectedly
enhances XVir-N-31 gene expression and subsequently viral genome
replication, particle formation, and oncolysis. At the molecular level,
this occurs via enhanced association of the adenovirus protein E1A12S,
present in XVir-N-31, with CDK9, an activator of RNA-Pol 2 elongation.
In contrast, BRD4 depletion by siRNA prevented adenovirus induced
S-phase progression, minimizing the enhancement of JQ1 on viral
replication.
Discussion: Here, we discovered that BRD4, unlike in other viruses, is
not directly involved in adenoviral gene expression but is necessary
for the induction of S-phase, which promotes adenoviral replication.
Furthermore, inhibition of BRD4-binding to acetylated histones by
JQ1, which facilitates E1A12S binding to CDK9, indicates that BRD4 is
involved in regulating the transactivation capacity of E1A-proteins.
Conclusion: Combining the oncolytic adenoviruses XVir-N-31 with
BRD4 inhibition oers a novel approach to enhance the lytic eect of
XVir-N-31 in a clinical setting.
Disclosure Statement: P.S.H. is co-founder of XVir erapeutics GmbH.
Disclosure Statement: e authors declare the following: P.S.H. is co-founder of
XVir erapeutics GmbH. All other authors declare no competing interests.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts178
1024
Combined targeting of bromodomain protein BRD4 and
RB /E2F axis leads to highly synergistic cell killing by YB-1
dependent oncolytic virus in HNSCC
Felicia Segeth1; Florian Klein2; Eva Magdalena Beck1; Klaus Mantwill2;
Jürgen Gschwend2; Roman Nawroth2; Andreas Kolk1; Per Sonne Holm1,2,3
1Department of Oral and Maxillofacial Surgery, Medical University Innsbruck,
Innsbruck, Österreich
2Department of Urology, Klinikum rechts der Isar, Technical University of
Munich, München, Deutschland
3XVirTherapeutics GmbH, München, Deutschland
Background: e entry of oncolytic viruses (OVs) into clinical applica-
tion opens groundbreaking changes in current and future treatment reg-
imens. However, despite their potent anti-cancer activity in vitro, clinical
studies revealed limitations of OVs as monotherapy. e same applies to
CDK 4/6 inhibitors (CDK4/6i) and BRD4 inhibitors (BETi) targeting the
cell cycle. In this study, we evaluated the anti-tumoral eect of XVir-N-31,
an YB-1 dependent oncolytic adenovirus, in combination with Ribociclib,
a CDK4/6 inhibitor, and JQ1, a BRD4 inhibitor, in vitro in a panel of
HNSCC cell lines.
Methods: HNSCC cell lines Cal33, Fadu and SAS were used. Ribociclib
was used as a CDK4/6- and JQ1 as BRD4 inhibitor. Replication and gene
expression of XVir-N-31 was measured by RT-qPCR, protein expression
by western blotting, and cell lysis by SRB assays. Furthermore, we per-
formed ChIP-PCR and RNA-Polymerase II activation assay to determine
RNA-Polymerase activity.
Result: Treatment with CDK4/6i and BRD4i increase viral gene expres-
sion, viral genome replication, particle formation and leads to highly syn-
ergistic cell killing of XVir-N-31 in infected HNSCC cells.
Discussion: Our data show that in spite of the opposing roles in aecting
the cell cycle, the combination of oncolytic adenovirus XVir-N-31 with
CDK4/6i & BETi acts highly synergistic in cancer cell lysis. Furthermore,
additional molecular analyses on this subject demonstrate that the pos-
itive transcription elongation factor P-TEFb plays a decisive role in this
regard.
Conclusion: e combination of CDK4/6i & BETi and XVir-N-31 is an
attractive strategy to achieve substantial cancer cell killing and is highly
suitable for clinical testing.
Disclosure Statement: e authors declare no conict of interest.
Novel Agents/Early Clinical Trials
Poster
690
ZENYTH-ESO Substudy 1 (GSK3901961), Cohort 1: a rst-in-
human study to assess the safety and recommended phase
II dose of next generation NY-ESO-1-specic TCR T-cells in
HLA-A*02 patients with non-small cell lung cancer
Martin Wermke1; Roland Ullrich2; Jerey Yachnin3; Stephan Mielke4;
Reema Patel5; Melinda L Yushak6; Adam J. Schoenfeld7; Jayesh Desai8;
Mehmet Altan9; Sandra P. D’angelo10; Jonathan Noujaim11;
John B.A.G. Haanen12; Benjamin Powers13; Thomas Faitg14; Wenlei Liu15;
Nitin Patel15; Dejka M. Araujo16
1Universitätsklinikum Carl Gustav Carus
2Klinikum der Universität Köln, Köln, Deutschland
3Karolinska University Hospital and Institutet, Karolinska Comprehensive Cancer
Center, Stockholm, Schweden
4Karolinska University Hospital and Institutet, Karolinska Comprehensive Cancer
Center, Stockholm, Schweden
5Markey Cancer Center, University of Kentucky, Lexington, USA
6Winship Cancer Institute at Emory University, Department of Hematology and
Medical Oncology, Atlanta, USA
7Memorial Sloan Kettering Cancer Center
8Peter MacCallum Cancer Centre, Melbourne, Australien
9MD Anderson Cancer Center
10Memorial Sloan-Kettering Cancer Center, New York, USA
11Institut D’Hématologie-Oncologie, Hôpital Maisonneuve-Rosemont
12Antoni van Leeuwenhoek Ziekenhuis
13University of Kansas Medical Center, Division of Hematology/Oncology,
Department of Internal Medicine, Kansas City, USA
14GlaxoSmithKline
15GlaxoSmithKline, Collegeville, USA
16MD Anderson Cancer Center, Manseld, USA
Background: Letetresgene autoleucel (lete-cel; GSK3377794) is an autolo-
gous T cell therapy expressing an anity-enhanced T cell receptors (TCR)
to improve recognition of cancer cells expressing NY-ESO-1 and/or
LAGE-1a. It is being evaluated in non-small cell lung cancer (NSCLC)
[1], where NY-ESO-1 and LAGE-1a expression occur in 20–30% and 16%
of tumors, respectively [2-3]. Additional modications are being incor-
porated into next generation cell therapies to improve therapeutic poten-
tial. GSK3901961 incorporates the same anity-enhanced T-cell receptor
as lete-cel and in addition expression of the CD8α chain to induce sta-
bilization of TCR-HLA class I interaction on CD4+ T cells to enhance
T-cell persistence and helper functions, and potentially enhance activity
of tumor-specic immune response.
Within a rst-in-human master protocol (NCT04526509, ZENYTH-
ESO), substudy 1 will investigate GSK3901961 in patients with advanced
non-small cell lung cancer.
Methods: Substudy 1 has two stages; initial dose conrmation and dose
expansion. Key eligibility criteria include age ≥18 yrs, Stage IV NSCLC.
Patients must be HLA-A*02:01, *02:05, or *02:06-positive, and express
NY-ESO-1/LAGE-1a on tumor biopsy. Patients with and without action-
able genetic aberrations are eligible if they have received ≥1 prior lines(s)
of standard of care therapy.
Primary endpoints: safety (adverse events) and tolerability (dose-
limiting toxicities). Secondary endpoints: investigator-assessed over-
all response rate, duration of response, maximum transgene expansion
(Cmax), Tmax, and AUC(0-t). Analyses will be descriptive. e master protocol
is open for recruitment.
Results: Funding: GSK (209012, NCT04526509).
Discussion: Previously presented at WCLC 2021.
Conclusions: is study is recruiting. is substudy will evaluate the
safety and ecacy of GSK3901961 in NSCLC.
References:
1. Reckamp KL, et al. Ann Oncol 2019;30(Suppl_5):v657–8
2. Gnjatic S, et al. Adv Cancer Res 2006;95:1–30
3. Kim YD, et al. Int J Mol Med 2012;29:656–62
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 179
Novel developments: Cytotoxic Chemotherapy
Poster
853
Local treatment of conjunctival melanomas using repetitive
electrochemotherapy – in vitro analysis of antitumor
eectiveness in 3D tumor models
Joana Heinzelmann1; Udo Siebolts2,3; Sarah Coupland4; Arne Viestenz1
1Universitätsklinikum Halle (Saale), Klinik für Augenheilkunde, Halle (Saale),
Deutschland
2Universitätsklinikum Halle (Saale), Institut für Pathologie, Halle (Saale),
Deutschland
3Universitätsklinikum Köln, Institut für Pathologie
4Liverpool of University, Molecular & Clinical Cancer Medicine, Vereinigtes
Königreich
Local treatment of conjunctival melanomas using repetitive elec-
trochemotherapy – in vitro analysis of antitumor eectiveness in 3D
tumor models
Authors: Joana Heinzelmann, Udo Siebolts, Sarah Coupland, Arne
Viestenz
Background: Conjunctival melanoma (CM) is a rare ocular tumor.
Despite dierent treatment options, CM has a high rate of local recur-
rences as well as a worse survival rate. Novel therapy options are needed
to improve the prognosis of CM.
Electrochemotherapy (ECT) is a combination of chemotherapy and
electroporation for local therapy of tumors. In treatment of various can-
cers like cutaneous melanoma and subcutaneous tumor lesions, ECT is a
promising clinical veried therapy. is study proved the eectiveness of
repetitive application of ECT on CM.
Methods: Tumor spheroids of three CM cell lines were treated repetitively
with ECT using chemotherapeutic agent bleomycin on day 3, 5 and 7 of
culture (3xECT). Application of bleomycin alone (CT) as well as electro-
poration alone (EP) served as controls. Cytotoxic eect was measured at
day 10 by determination of viability, spheroid growth, proliferation capac-
ity and apoptosis induction. Spheroid outgrowth rate was measured up to
80 days of reculturing.
Result: Compared to controls, spheroid size and viability was signi-
cantly reduced aer 3xECT treatment. 3xECT treatment of CM spher-
oids is associated with decreased proliferation capacity (down to 8%) and
increase in apoptotic cells. In the majority of 3xECT treated spheroids,
no viable and proliferating cells were detected. Only 30-40% of 3xECT
treated spheroids exhibited single outgrowing cells and thereby, with a
delay of time up to 38 days.
Discussion: 3xECT application eectively induce cytotoxic eect on CM
spheroids via inducing apoptosis, inhibition of proliferation and conse-
quently a small percentage of surviving tumor cells. Further studies are
needed to establish a CM adapted ECT protocol.
Conclusion: ese data supports the hypothesis that 3xECT results in an
improved antitumor eectiveness in CM and could be used as alternative
therapy option.
Disclosure Statement: e authors declare no conict of interest.
983
Development of halido(NHC)gold(I) complexes as antitumor
agents: Investigations on the reactivity with components of
cellular medium and their inuence on cytotoxicity
Paul Kapitza; Amelie Scherer; Ronald Gust
Universität Innsbruck, Pharmazie, Pharmazeutische Chemie, Innsbruck,
Österreich
Background: Auranon represents a gold(I)-containing drug that was
approved in 1985 for the treatment of rheumatoid arthritis. e primary
mode of action postulated for Auranon involves its property to disrupt
the reduction/oxidation system within the cell. erefore, the complex
also causes unspecic cytotoxic eects in malignant and non-malignant
cells.
Methods: In order to increase the tumor selectivity, N-heterocyclic car-
bene (NHC) complexes of the halido(NHC)gold(I) (halido = Cl- 1, Br- 2,
I- 3) and [(NHC)2Au(I)]+ (4) type were developed and tested for anti-
tumor activity in vitro against numerous wildtype and corresponding
resistant cancer cell lines (A2780, A549, MCF-7, K562). We analyzed the
components in cell medium and studied the reaction with (NHC)gold(I)
compounds 1-4 using HPLC experiments.
Result: e compounds showed improved (4-fold) ecacy on the cispla-
tin-resistant ovarian cancer cell line A2780cis (IC50: Cisplatin (9.80 µM)
> 1 (4.97 µM) > 2 (3.95 µM) > 3 (0.45 µM) > 4 (0.03 µM)) compared
to A2780wt. Furthermore, the cytotoxic eects were only marginally in
non-cancerous SV-80 cells. e gold complexes interact very fast with thi-
ol-containing molecules. Complete replacement of the halogen at the gold
center in physiological NaCl solution yielding the chlorido(NHC)gold(I)
was demonstrated for 2 and partially for 3. e latter underwent also a
ligand scrambling to the higher active 4. e reaction products were iso-
lated and their participation on the cytotoxic eect was conrmed.
Discussion: As other metal-based drugs, the complexes interact with
intracellular targets upon ligand exchange reactions. Already in cell cul-
ture medium potential nucleophiles are present. If the complexes are
transformed in the medium prior to the cellular uptake, the antitumor
eects cannot be ascribed to the original complex.
Conclusion: e data from this study clearly demonstrate that the assess-
ment of the biological activity of gold(I) complexes in tumor therapy has
to be done with care, because degradation products participate on the bio-
logical activity.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts180
Nursing in Oncology
Poster
49
Implementierung einer Advanced Practice Nurse (APN) im
Brustzentrum des LMU Klinikums München
Kristina Lippach1; Inge Eberl1; Rachel Würstlein2
1Stabsstelle Personalentwicklung und Pegewissenschaft, LMU Klinikum
München, München, Deutschland
2Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, LMU Klinikum
München, Brustzentrum und CCC München, München, Deutschland
Background: Der Einsatz von oralen Tumortherapien führt zu veränder-
ten Versorgungsbedarfen und zu Veränderungen im pegerischen
tigkeitsfeld.
Methods: Mittels Evaluationsstudie im Mixed-Methods-Design wurden
die Perspektiven von Pegenden, Ärztinnen und Patientinnen zu Eekten
einer APN-Rolle erhoben. Als patientenbezogene Outcomes wurden in
einem prä-post-Design die gesundheitsbezogene Lebensqualität und die
Informiertheit mittels EORTC-QLQ-C30 und EORTC-QLQ-INFO25
betrachtet.
Result: Herausfordernd in der Implementierung waren die
Akzeptanz der neuen Pegerolle, die Einbindung in ärztliche und
pegerische Versorgungsstrukturen und die Auswahl erweiterter
Pegetätigkeiten. Patientinnen mit APN schätzten die Zufriedenheit
mit Versorgungsprozessen, dem Nebenwirkungsmanagement und der
psychosozialen Betreuung positiver ein. Informationen zur Behandlung
(t0=64,02, t1= 74,18), weiterführende Versorgungsangebote (t0=45,38,
t1= 65,69), Möglichkeiten des Selbstmanagements (t0=59,70, t1= 82,35)
und Zufriedenheit mit Informationen (t0=73,85, t1= 90,19) wurden in der
APN-Gruppe deutlich besser bewertet.
Discussion: Während die Rolle der APN bei Ärzten und Patientinnen
akzeptiert wurde, zeigten die Pegenden deutliche Vorbehalte, die
sich negativ auf die intraprofessionelle Kooperation auswirkten.
Patientenbezogene Outcomes, wie Zufriedenheit und Informiertheit,
wurden analog vorheriger Studien deutlich positiver bewertet als ohne
APN. Patientinnen waren anfangs skeptisch gegenüber der Betreuung
durch eine APN, was sich im Verlauf veränderte hin zu Akzeptanz und
Wertschätzung.
Conclusion: Die patientenbezogenen Eekte zeigten, dass das
Implementierungsziel mit der APN erreicht wurde. Perspektivisch kann
die APN durch ihre Kompetenzen und ihre Arbeitsweise einen Beitrag
zur Patientenzufriedenheit und -sicherheit aber auch zu organisatio-
nalen Entwicklungen, wie dem Magnet-Gedanken leisten. Gerade in
der Onkologie bildet eine spezialisierte APN ein optimales Bindeglied
zwischen allen Beteiligten.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
90
Onkologische Pege zwischen Fachlichkeit,
Qualitätsanforderungen und Pegemanagementstrategien in
der Uniklinik Köln
Johannes Bösche1; Dennis Nano1; Barbara Starbatty2; Steen Krebs2;
Barbara Strohbücker3
1Uniklinik Köln, Pegedirektion, Pegedienstleitung Allgemeinpege, Köln,
Deutschland
2Uniklinik Köln, Centrum für Integrierte Onkologie (CIO) Aachen Bonn Köln
Düsseldorf, Köln, Deutschland
3Pegedirektion, Stabsabteilung Pegepraxis und Entwicklung, Köln,
Deutschland
Background: Fachweitergebildetes Pegepersonal für alle Abteilungen des
Onkologischen Zentrums zu gewinnen und die Zertizierungsvorgaben
zu erfüllen stellen angesichts des Personalmangels eine permanente
Herausforderung dar. Um Rahmenbedingungen und Umsetzung sicher-
zustellen, ist eine enge Zusammenarbeit von Fachpege, Qualitäts- und
Pegemanagement wichtig.
Methods: In Jour Fixen von Fachpege, QM und Pegemanagement
werden Probleme und Ergebnisse aus Audits, Patientenbefragungen
und Praxis analysiert und Lösungsstrategien erarbeitet. Zur klinikweiten
pegefachlichen Versorgung wird eine Kombination aus zentraler und
dezentraler Expertenstruktur mit eigenen Aufgabenprolen entwickelt.
Result: Wichtigstes Ergebnis dieser Zusammenarbeit ist das Modell einer
Kombination aus zentraler und dezentraler Personaleinsatzstruktur.
Hierfür wurden Aufgabenprole, Rahmenbedingungen und Strukturen
entwickelt. Die Zentrale Onkologische Fachpege wird dezentral in den
Krebszentren um onkologische Pegeexperten erweitert. Sie sollen als feste
Ansprechpartner für die Patienten entlang des Behandlungspfades fungi-
eren. Darüber hinaus konnten Pegevisiten und Fallbesprechungen nach-
haltig implementiert werden und stellen die Zertizierungsanforderungen
sicher.
Discussion: Die Zusammenarbeit von Fachpege, QM und
Pegemanagement fördert das gegenseitige Verständnis und erö-
net Handlungsspielräume. Die Kombination aus zentral und dezen-
tral eingesetzten Pegeexperten, ermöglicht eine ächendeckende
Patientenversorgung nach aktuellem Stand des Wissens. Verbindlichkeit
in Bezug auf Rolle und Aufgaben stärkt die Arbeitszufriedenheit.
Conclusion: Ein funktionierendes Netzwerk zwischen Fachpege,
Qualitäts- und Pegemanagement steuert zentral und steht im kontinui-
erlichen Dialog mit den Krebszentren. Die enge Zusammenarbeit scha
nachhaltig pegerische Rahmenbedingungen, die eine fachpegerische
Versorgung der onkologischen Patienten in konservativen und operativen
Bereichen sicherstellen.
Disclosure Statement: e authors declare no conict of interest.
200
Improving the quality of oncological care at the University
Krukenberg Cancer Center Halle (KKH) through oncological
nursing visit (ONV)
Jana Tietl; Lysanne Götze; Susann Schulze; Haifa Kathrin Al-Ali
Krukenberg Krebszentrum Halle, Universitätsklinikum Halle, Halle (Saale),
Deutschland
Introduction: e Oncological Center (KKH) of the University Hospital
Halle (UKH) is certied by the German Cancer Society since 2017. To
improve in-patient (pat) oncology care, ONVs were established. We pres-
ent the impact of ONVs on pat management in the Head and Neck Cancer
(HNC) Center of the KKH.
Methods: ONVs were established in 2018 as a centralised digital council
service of the KKH for all nurses caring for cancer pats at the UKH. In the
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 181
presence of ward nurses, ONVs were conducted at the bedside by certied
KKH oncological nurses. Each pat was handed a folder with all facets of
cancer care. is analysis includes 236 pats with head and neck tumors
from 2019 and 2020. Pats who received ONVs (n=96; group A) were com-
pared to pats without ONVs (n=147; group B).
Results Pat characteristics were similar in the two cohorts in terms of age
[median 63.5 (range 40-95)] years (y) for A vs 64, (range 43-90) y for B
and the Karnofsky Index (80%, in A vs 90%, in B. Group A included 87/96
(91%) newly diagnosed and 9% relapse/refractory pat. Similarly, in B
129/147 (87%) pat were newly diagnosed and the remaining 18 pats were
suering from relapse/refractory HNC. Although symptoms were doc-
umented by the standard nursing sta, in the ONVs further less specic
symptoms could be revealed. Dry mouth, loss of appetite, fatigue, psycho-
logical problems, and emotional distress were documented in 95%, 39%,
40%, 95%, and 32% In A vs 19%, 1%, 7%, 38%, and 7% in B, respectively.
With ONVs, more detailed advise and management tips for pat regarding
dierent medical problems such as tracheostoma, PEG, mouth, and skin
care could be given. Additionally, psychological support could be oered
to 98% of pats in A compared to 34% in B. Contact to pat advocacy groups
was also possible.
Conclusions With the implementation of ONVs, a high level quality of
cancer care is possible. Sucient time and extra qualied personal res-
sources allow a much closer look to the individual pat, the identication
of physical and mental needs, and the initiation of the appropriate mea-
sures. e impact of ONVs on long-term outcome of cancer needs to be
analysed.
Disclosure Statement: e authors declare no conict of interest.
472
Onkologische Pegevisiten an der Chirurgischen Klinik am
UKHD
Romy Fiedler1; Claudia Ohlrogge1
1Universitätsklinikum Heidelberg, Chirurgische Klinik, Arbeitsgruppe
Onkologische Pege, Heidelberg, Deutschland
Background: Im Rahmen der Zertizierung als onkologisches
Fachzentrum wurde an der Chirurgischen Klinik des
Universitätsklinikums Heidelberg die Arbeitsgruppe (AG) Onkologische
Pege gegründet, um die pegerische Versorgung onkologischer
PatientInnen weiter zu verbessern. Ein wichtiges Instrument dabei stellen
onkologische Pegevisiten dar.
Methods: Die AG besteht aus 5 erfahrenen Fachgesundheits- und
KrankenpegerInnen für Palliative Care und/ oder Onkologie. Einmal
pro Woche visitiert eine Pegekra PatientInnen mit potenziellem und
bestehendem onkologischem Beratungsbedarf. Schwerpunkte hier-
bei sind neben der persönlichen Krankheitsbewältigung emen wie
weitere erapiemöglichkeiten, Ernährung, Schmerztherapie oder
auch die Anbindung an ambulante Palliativteams. Des Weiteren stellt
die Pegevisite eine Schnittstellenverknüpfung im interdisziplinären
Teamdar.
Result: In den letzten zwei Jahren konnten über 90 onkologische
Pegevisiten durchgeführt werden. In 2/3 der Fälle wurde zu pegerel-
evanten emen beraten. 1/3 der Visiten dienten als erleichternde
Gespräche ohne beratende Inhalte.
Discussion: Chirurgische PatientInnen können von onkolo-
gischen Pegevisiten protieren. Der Erfolg hängt u.a. vom
Zustand der Betroenen am Visitentag sowie dem Grad der
Krankheitsverarbeitungab.
Conclusion: Onkologische Pegevisiten sind ein Instrument zur
Ermittlung von Unterstützungsbedarf und zur Abstimmung pegerischer
Ziele und Maßnahmen. Dabei können aktuelle Pegeprobleme, notwen-
dige Maßnahmen für die Zeit nach der Entlassung oder die persönliche
Belastung thematisiert werden.
Indication of source
1 Lippach, K; Kelber, S; Gutekunst, S (2018): Onkologische Pegevisite und
Fallbesprechung – praktische Umsetzung. Onkologische Pege, 4: 48–54
2 Maio, G (2020): Zuwendung als Heilmittel gegen das Leiden. Dem leidenden
Menschen begegnen. CNE.fortbildung 2020; 13: 10-12
Disclosure Statement: e authors declare no conict of interest.
494
Aromapege: Rosenhydrolat zur Hautpege unter
Strahlentherapie
Bettina Noack1; Renate Fuhr2
1Tübingen, Radioonkologie, Pegeambulanz, Tübingen, Deutschland
2Universitätsklinikum Tübingen, Pegedirektion, Tübingen, Deutschland
Purpose: Unter Strahlentherapie pegen viele Patient*innen ihre
Haut intensiv mit fetthaltigen Salben und verstärken so ungewollt
durch „Überpegung“ häug das dermatologisch therapiebedingte
Krankheitsbild. Bei der Verwendung von Rosenhydrolat ist bekannt,
dass es die Hauttoxizität durch seine entzündungshemmenden und
wundheilenden Eigenschaen verringert und der Wohlgeruch das
Allgemeinbenden während der Strahlentherapie unterstützen kann.
Methods: In der radioonkologischen Pegeambulanz (PA) des
Universitätsklinikums Tübingen wurden n=27 Tumorkranke in einer
Anwendungsbeobachtung (AWB) mit Rosenhydrolat (RH) untersucht.
Nach unauälligem Armbeugentest – wurde das RH 3-4 x täglich im
Bestrahlungsgebiet angewendet. Zusätzliche Hydrierung durch Cremes
oder Öle war bei Bedarf möglich. Parameter: RT-Hauttoxizität, Wohlgefühl
Haut, psychisches Wohlbenden und Besserung des Juckreizes.
Results: 100% (n=27) der Erkrankten empfanden den Du des RH´s
als angenehm. Bei allen war der Armbeugentest nach der Anwendung
negativ. 70,4% (n=19) empfanden die Anwendung als angenehm für
Haut und Psyche. 51,9% (n=14) der Anwender*innen verspürten eine
Verbesserung des Juckreizes. 25,9% (n=7) der Patient*innen brachen die
Anwendung bei einer RT Toxizität EORTC/RTOG in St. 3 ab. 29,6% (n=8)
der Patient*innen stellten sich nicht mehr in der PA vor.
Discussion: Aufgrund der sehr kleinen und heterogenen Stichprobe sind
die Ergebnisse nur eingeschränkt aussagekräig; die AWB zeigt jedoch
tendenziell ein vielversprechender Outcome, bei der ebenfalls überwieg-
end über die traditionelle, nicht-evidenzbasierte Anwendung von RH in
der Literatur berichtet wird.
Conclusion: In der AWB zeigte die Applikation von RH im
Bestrahlungsfeld vorwiegend positive Ergebnisse. Für ein repräsenta-
tives Ergebnis ist eine umfassendere Studie erforderlich, die derzeit in
Planungist.
Disclosure Statement: e authors declare no conict of interest.
642
Detecting Stress and Stressors at the Workplace in Palliative
Care – The DiPa Study
Aaron Seehausen1; Carolin Schneider1; Wencke Chodan2; Florian
Höpfner2; Hugo Murua Escobar1; Christian Junghanß1; Mario Aehnelt2
1Rostock, Department of Medicine, Clinic III – Hematology, Oncology, Palliative
Medicine; Rostock University Medical Center, Rostock, Deutschland
2Rostock, Fraunhofer Institute for Computer Graphics Research, Rostock,
Deutschland
Background: Nurses in palliative care are exposed to particular stress
through confrontation with grief, dying and death. As a result, they are
at higher risk for physical or mental disorders such as burnout. e gen-
eral and individual causes are not well researched. e DiPa study aims at
nding and reducing typical stressors in a palliative care unit.
Methods: Nurses at the palliative care unit of the Rostock University
Medical Center were voluntarily enrolled. ey were equipped with a wrist
band to continuously measure bioparameters in combination with record-
ing environmental parameters through additional technical equipment.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts182
Data was generated during each work shi for 6 weeks. ese objective
data are analyzed together with subjective perceptions gathered once (via
a 137-items-study questionnaire and the Maslach Burnout Inventory),
repeatedly (via interviews) or continuously (via ecological momentary
assessments).
Results: e sample consisted of 12 nurses (out of 18; participation rate
66.7 %) aged 22 to 53 years (mean age 34 years). Bioparameters can be
evaluated in 185 complete (66.3 %) and 25 partial shis (9.0 %) out of a
total of 279 shis. Among the rst 6 participants, the total perceived strain
ranged from 7.6 to 15.1 out of 54 possible points in the study question-
naire which suggests a low burden. Within the workplace, the most fre-
quent stressors were stressors related to patients or their relatives, which
were, however, rated as less weighty than stressors related to job structure
and work organization.
Discussion: e acceptance across all participants was high. First data
hint at the methodical and technical eectiveness of the DiPa approach.
However, not all collected data have been analyzed yet. A thorough analy-
sis of particular stressors is currently ongoing and will be presented later.
Conclusion: is innovative study shows the feasibility of using wearable
devices in combination with subjective instruments to measure stress in
palliative care nurses.
Disclosure statement: e project is funded by the Federal State of Mecklen-
burg-Western Pomerania.
660
Patients’ experiences and needs undergoing immune-
checkpoint-inhibitor therapy – A qualitative study
Laura Püschel1; Anne Letsch2; Anne Christin Rahn1; Stefanie Mentrup1
1Institute for Social Medicine and Epidemiology, Nursing Research Unit,
University of Lübeck, Lübeck, Deutschland
2Department of Medicine II, Hematology and Oncology, University Hospital
Schleswig-Holstein, Kiel, Deutschland
Background: People treated for cancer with immune checkpoint inhibi-
tor (ICI) therapies may develop immune-related adverse events (irAEs).
IrAEs can occur at any time with variable clinical presentations and should
therefore be assessed regularly. is qualitative study aimed to explore the
experiences of people with cancer (PwC) undergoing ICI therapy with a
focus on self-management, educational and further needs.
Methods: Semi-structured interviews were conducted with PwC who
received or discontinued ICI therapy. Interviews were audio-recorded,
transcribed verbatim and analyzed thematically.
Results: irteen people (7 women, 6 men) with dierent cancer diag-
noses receiving ICI as mono- or combination therapy participated in the
interviews. ree overarching themes were identied: (1) In a state of
uncertainty: life between hope and fears, (2) continuity as a basis for good
care, (3) spectrum of side eects: impact on self-management and needs.
PwC interviewed, oen found themselves in a state of uncertainty regard-
ing the future course of their illness. In this context, ICI therapy is oen
regarded as the last chance to prolong life. erefore, most of the PwC
prefered passive and fast decision-making. Some interviewees described
that irAEs caused uncertainty and impacted individual information and
support needs as well as self-management. Continuity of care relieved
most PwC interviewed here. In this regard, interviewees described the
benets of a qualied, accessible, and xed contact person.
Discussion: PwC undergoing ICI therapy might benet from a healthcare
professional who supports the treatment trajectory and helps recognizing
irAEs early. Information should be delivered individually according to the
persons’ needs.
Conclusion: is study indicates that uncertainty, irAEs and continuity
of care inuence the needs and self-management of PwC undergoing ICI
therapy. Support programs should consider continuity of care and other
contextual factors of PwC and ICI therapy.
Disclosure Statement: e authors declare the following: Honorare: BMS, Jannsen
Cilag, MSD, Roche, Tesaro; Grünenthal, Astra Zeneca. Novartis, Merck Serono;
Finanzierung wissenschalicher Untersuchungen: Novartis, Tesaro; Andere
nanzielle Beziehungen: Servier; Immaterielle Interessenkonikte: Beisitzerin im
Vorstand der DGP
692
Creating evidence for naturopathic nursing interventions in
oncology – a systematic approach
Regina Stolz1; Nadja Klafke2; Birgit Kröger1; Ursula Boltenhagen3;
Anna Kaltenbach3; Rolf Heine4; Christel Idler5; Monika Layer6; Sara Kohler7;
Marcela Winkler5; Petra Voiss8; Stefanie Joos1; Cornelia Mahler3
1Institute for General Practice and Interprofessional Care, University Hospital
Tuebingen, Tübingen, Deutschland
2Health Services Research and Implementation Science, Department of
General Practice and Health Services Research, University Hospital Heidelberg,
Heidelberg, Deutschland
3Institute of Health Sciences, Department of Nursing Science , University
Hospital Tuebingen, Tübingen, Deutschland
4Anthroposophic Nursing Network, Academy of Anthroposophic Nursing
Professions at the Filderklinik, Filderstadt, Deutschland
5Robert-Bosch-Krankenhaus Stuttgart, Stuttgart, Deutschland
6Department of Integrative Medicine and Department of Nursing Development,
Cantonal Hospital St. Gallen, Schweiz
7Programm director of MAS in Oncological Nursing, Zurich University of Applied
Sciences, Winterthur, Schweiz
8Department of Internal and Integrative Medicine, Evang. Kliniken Essen-Mitte,
Faculty of Medicine, University of Duisburg-Essen, Essen, Deutschland
Background: Nurses working in oncology use a wide range of naturo-
pathic interventions in their daily practice to alleviate symptoms and
improve the quality of life of oncological patients. However, there is no
external evidence for many of these interventions. Due to a lack of sci-
entic studies in the eld, the aim of the project is to develop a standard-
ized procedure to generate evidence on naturopathic interventions, which
enable to draw recommendations for nursing practice.
Methods: e systematic procedure was developed by the working group
(WG) Integrative Nursing in Oncology over a period of four years, in an
iterative process. e process is based on the experience of the expert
panel members in the development of guidelines and/or quality instru-
ments such as practice standards.
Result: e systematic methodological approach consists of three succes-
sive steps where internal and external evidence have been combined: a
scoping review, a structured consensus process (cp) with oncology nurses
to collect and evaluate naturopathic interventions, and a further supple-
mentary literature review based on additional ndings within the cp. e
procedure was successfully carried out for mucositis, insomnia, fatigue,
hand-foot syndrome and chemotherapy-induced poly-neuropathy.
Discussion: e procedure represents a successful theory-practice trans-
fer through structured cooperation between (nursing) scientists and
nursing practitioners. e recommendations for practice developed in
the process can be classied in the AWMF classication between an S1
guideline (informal consensus of an expert group) and an S2e guideline
(evidence-based).
Conclusion: rough the step-by-step synthesis of internal evidence with
the best available external evidence, the evidence base for naturopathic
nursing interventions in oncology can be generated and recommenda-
tions for practice derived.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 183
Oncological Pharmacy
Best-of-Abstract-Vortrag
754
Pharmacist in a Multiprofessional Cancer Care Team in
Germany – Benets Resulting from the Work of an Oncology
Ward Pharmacist
Svenja Dierkes1; Annette Freidank1; Carsten Culmsee2; Roland Radziwill1
1Klinikum Fulda gAG
2Institut für Pharmakologie und Klinische Pharmazie , Philipps-Universität
Marburg, Marburg, Deutschland
Background: Due to high numbers of newly diagnosed cancer patients
and increasing complexity of new chemotherapeutics, there is an increas-
ing demand for better management of patients. Pharmacists are able to
ensure the patients safety and quality of life.[1]
e objective of this intervention study is to evaluate the benet of
a pharmacist embedded in a multiprofessional cancer care team on an
oncology ward in Germany.
Methods: e present study is a single-centered, controlled, retrospective,
and prospective intervention study consisting of three dierent phases
P0, P1, and P2. e phases dier regarding the underlying type of data, the
duties of the pharmacy, and the employment of a ward pharmacist (P1 and
P2). In the rst phase (P0), two clinical pharmacists independently identi-
ed all medication errors (MEs) which they detected from archived med-
ical le. For the second and third phase, an electronic patient record has
been implemented and the ward pharmacist determined, documented,
and solved MEs as part of her daily work. In all phases, the classication
as ME was set only aer conrmation by an oncologist to ensure clinical
relevance.
Result: e three phases with 52, 46, 50 patients, respectively, were com-
parable regarding the baseline characteristics. For better comparability the
MEs refer to the number of medication lines which comply with one drug
per day. e statistical analysis showed a signicant reduction of clini-
cally relevant MEs (P0: 33 MEs/ 100 medication lines vs. P1: 7 MEs/ 100
medication lines vs. P2: 2 MEs/ 100 medication lines; (p < 0,001)) for the
three phases.
Conclusion: e implementation of a ward pharmacist had a signicant
impact on the reduction of MEs consequently increasing the patients
safety.
Indication of source
1 E. M Segal, et al . J Oncol Pharm Pract 2019
Disclosure Statement: e authors declare no conict of interest.
Poster
655
Evaluation of knowledge, usage behavior and user
expectations of an oral anticancer drug database and
information system – qualitative cognitive pretesting with
dierent types of target groups
Sahra Kießig1; Tessa Richter1; Ste Chalas1; Klara Gren2;
Holger Muehlan2; Franziska Ockert-Schön3; Michael Höckel4;
Christoph Ritter1
1Institut für Pharmazie, Universität Greifswald, Klinische Pharmazie, Greifswald,
Deutschland
2Institut für Psychologie, Universität Greifswald, Gesundheit & Prävention,
Greifswald, Deutschland
3Deutsche Gesellschaft für Onkologische Pharmazie, Projektmanagement Oralia
Initiative, Hamburg, Deutschland
4Gesundheit Nordhessen Holding AG, Zentralbereich Apotheke, Kassel,
Deutschland
Background: e use of oral anticancer drugs requires close attendance
by health care professionals. Information systems exist that are intended
to support patient care. e aim of this study is to evaluate knowledge,
usage behavior and expectation of the Oralia oral anticancer drug data-
base among members of the German Society of Oncological Pharmacy
(DGOP) with a focus on interdisciplinary exchange.
Methods: A questionnaire was developed on knowledge, usage behavior
and expectations of the Oralia database. Pretesting was conducted among
three groups of potential users. e survey will be sent to all members of
the DGOP. e answers will be analyzed using descriptive statistics.
Result: Pretesting was conducted with pharmacy students (n=3), mem-
bers who do not know the database (n=3), members who know but do not
use the database (n=3), and recent and current users (n=6). Main issues
were unspecic descriptions of processes when using the database, illog-
ical order of possible answers, and inconsistent wording. Some aspects
were missing such as educational needs. e questionnaire was adapted
accordingly. All participants agreed with content and length.
Discussion: Subsequent adaptation of the questionnaire improved read-
ability and comprehensibility with no relevant extension of the question-
naire. e nal questionnaire contains ve sections that address (I) usage
conditions, (II) expectations and demands on the database, (III) expecta-
tions and demands on the patient management tool of the database, (IV)
improvements and future use, and (V) demographic data. For members
that do not know the database or know the database but do not use it the
questionnaire consists of sections I, V and selected questions from section
II. Previous and current users will receive the complete questionnaire.
Conclusion: Results of the survey will be presented during the meeting.
Results of this evaluation will provide better insights into and improve the
usage of the Oralia database and ultimately patient care.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts184
Other Topics
Poster
171
Vaccination status of oncological patients under treatment;
preliminary baseline data of the Easy Vaccination in Oncology
(EVO) Study
Katrin Trostdorf1; Nicola Delmastro2; Arne Gerrit Salomon3;
Maria Duran Cortes2; Mark Reinwald4; Christian Scholz5;
Ernst Späth-Schwalbe6; Veit Mannsmann7; Maike de Wit2;
Til Ramon Kiderlen1
1Vivantes Klinikum Neukölln, Klinik für Innere Medizin - Hämatologie, Onkologie
und Palliativmedizin, Berlin, Deutschland
2Vivantes Klinikum Neukölln, Innere Medizin - Kardiologie, Angiologie,
Nephrologie und konservative Intensivmedizin, Berlin, Deutschland
3Vivantes Klinikum Neukölln, Klinik für Innere Medizin - Pneumologie und
Infektiologie, Berlin, Deutschland
4Medizinische Hochschule Brandenburg - Theodor Fontane, Innere Medizin -
Klinik für Hämatologie und Onkologie, Brandenburg, Deutschland
5Vivantes Klinikum Am Urban, Klinik für Innere Medizin - Hämatologie und
Onkologie, Berlin, Deutschland
6Vivantes Klinikum Spandau, Klinik für Innere Medizin - Hämatologie, Onkologie
und Palliativmedizin, Berlin, Deutschland
7Vivantes Humboldt-Klinikum, Klinik für Innere Medizin - Onkologie, Berlin,
Deutschland
Introduction: e German Standing Committee on Vaccination
(STIKO) recommends vaccinations for oncological patients
(Bundesgesundheitsblatt 2020). ere is no public data on vaccina-
tion rates for these patients, but health insurance data suggest low rates
(Schmedt et al. 2017).
Methods: e EVO study was an interventional study to increase vaccina-
tion rates in oncology. For this abstract we analyzed the vaccination status
of oncological patients under treatment of the baseline, hence non-inter-
ventional, population. Data collection was conducted in 4 Medical Care
Centers (MCC) in Berlin, Germany (Jan - Nov 2020). All eligible patients
were asked to present their vaccination card. Only up-to-date vaccinations
were counted as valid. Missing vaccination cards counted as unvaccinated.
Results: Of 448 contacted patients, 242 (54,0%) were included; 151
(33,7%) did not respond. 55 (12,3%) patients were excluded. 177 (73,1%)
included patients provided their vaccination card; 65 (26,9%) could not
make a vaccination card available.
We found moderate rates for vaccinations against tetanus (51,2%), diph-
theria (48,8%) and pertussis (43,4%). Hepatitis B vaccination rates were
signicantly lower (15,7%) as were the rates for inuenza, with 25,2%.
Vaccination rates against pneumococci were even lower: 5,4% received
sequential vaccination with Prevenar13® and Pneumovaxx23®, 7,9% were
vaccinated with Prevenar13® only and 21,9% with Pneumovaxx23® only.
Similarly low vaccination rates were documented for meningococci, with
3,7% (Typ C) and herpes zoster, with 2,9%.
Conclusion: Our data show unsatisfactory low vaccination rates for
oncological patients. Dierent reasons are suspected to contribute to this
outcome, including lack of knowledge regarding vaccination by the oncol-
ogist and uncertainties regarding the underlying condition by the vacci-
nating physicians (Orange et al. 2012). ere is an urgent need to improve
communication between oncologists and family doctors, to target these
shortcomings.
Disclosure Statement: e authors declare no conict of interest.
198
A Multidisziplinary Analysis of Informed Consent Forms of
Clinical Trials in Hematology
Susann Schulze1; Nadja Jäkel2; Christin Naumann2; Marion Hackl1;
Sandra Ehlert1; Marcus Bauer3; Ute Berndt4; Petra Büchner-Steudel5;
Timo Faltus6; Katharina Jenner1; Kerstin Junghans7; Eva Kantelhardt4;
Christiane Ludwig5; Rose C.K. Moritz8; Adrienne Neustadt1; Andre Nowak9;
Bastian Ignaz Preissler1; Fana-Lamielle Samatin1; Jan Schildmann9;
Heike Schmidt10; Sandra Schönburg11; Stefanie Stegmann5; Janine Stingl1;
Hans Zillmann12; Haifa Kathrin Al-Ali1
1University Hospital Halle, Krukenberg Cancer Center Halle (Saale), Halle (Saale),
Deutschland
2University Hospital Halle, Department of Hematology/ Oncology, Deutschland
3Institute of Pathology, University Hospital Halle, Halle (Saale), Deutschland
4University Hospital Halle, University Clinic and Outpatient Clinic for
Gynecology, Halle (Saale), Deutschland
5University Hospital Halle, Department of Internal Medicine Gastroenterology/
Pneumology, Halle (Saale), Deutschland
6Faculty of Law and Economic Sciences, Martin-Luther-University Halle-
Wittenberg, Halle (Saale), Deutschland
7Martin-Luther-University Halle-Wittenberg, Faculty of Law and Economic
Sciences, Halle (Saale), Deutschland
8University Hospital Halle, University Clinic and Outpatient Clinic for
Dermatology and Venereology, Halle (Saale), Deutschland
9Institute for History and Ethics of Medicine, Interdisciplinary Center for Health
Sciences, Medical Faculty, Martin Luther University Halle-Wittenberg, Halle
(Saale), Deutschland
10University Hospital Halle, University Clinic and Outpatient Clinic for
Radiotherapy, Halle (Saale), Deutschland
11University Hospital Halle, University Clinic and Outpatient Clinic for Urology,
Halle (Saale), Deutschland
12Interdisciplinary Centre for Medicine, Ethics, Law, Martin-Luther-University
Halle-Wittenberg, Halle (Saale), Deutschland
Introduction: Clinical trials (CT) are regulated by Good Clinical Practice
(GCP) (Directive 2001/20/EC). For an independent patient (pt) deci-
sion-making, the informed consent form (ICF) is essential. We evaluated
ICFs from pt, healthcare professional, ethical, and legal perspectives.
Methods: ICFs of 38 hematologic CTs conducted at the University
Hospital Halle from 2005 and 2020 were included. Each sponsor- and
year-blinded ICF was independently evaluated by pts, physicians (Phy),
psycho-oncologists (Psy), legal professionals (Law), and ethicists (Eth)
based on a catalogue of 62 questions in 6 categories (Cat) [readability/
comprehensibility (A), CT details (B), benets/risks (C), personal data
protection (D), self-determined decision of pts (E), declaration of con-
sent (F)]. Rating options were optimal, unavailable/too-little, too-much,
and "cannot answer". Finally, each ICF was graded from 1 (very good)
to 6 (unsatisfactory). Each panelist evaluated a median of 5 ICFs with a
median length of 27 pages per ICF.
Results: From the 12799 possible answers, 3% were missing. Overall, only
31% (19/62) of questions were rated as optimal by >75%. Across all Cat
and in particular in Cat B and C, healthcare professionals rated similarly
or more critically compared to pts, Eth or Law. e majority of panelists
agreed that ICFs missed gures and summaries in Cat A. Rating discrep-
ancies were evident in Cat B between pts and Law/Eth [optimal 74% and
72% vs. too- little 56% and 51% respectively]. Cat C with 59% received
the lowest optimal rating mainly due to critical ratings by healthcare pro-
fessionals. Unexpectedly, 82% of pts and Law rated Cat D as optimal vs.
only 65% by Eth. Cat E was the only Cat were pts rated lower than other
panelists. Pts criticized the lack of an individual language and space for
remarks. Cat F was unproblematic with an optimal rating of 84%. Overall,
ICFs received a median grade of 2 (range 1-6). Psy were most judgmental
with a median grade of 3.
Conclusions: Our data show that although ICFs full the GCP require-
ments, there is substantial room for improvement in the interest of pts.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 185
272
Prevalence of idiopathic multicentric Morbus Castleman in
patients suering from cervical lymphadenopathy
Michael Krokenberger1; Kristina Schwamborn2; Ulrich Straßen1
1Klinikum rechts der Isar der Technischen Universität München,
Otorhinolaryngology / Head and Neck Surgery, München, Deutschland
2Klinikum rechts der Isar der Technischen Universität München, Institute of
Pathology, München, Deutschland
Background: Idiopathic multicentric Morbus Castleman (iMCD) is a
very rare disease with a broad spectrum of symptoms and a complex his-
topathological diagnosis. An expert meeting in 2017 dened new criteria
for the diagnosis for iMCD. It is estimated that in the US there are about
2-20 cases per one million patient years. Estimations for the German pop-
ulation do not exist yet. As lymphadenopathy oen occurs primarily in
the head and neck region patients are frequently referred to the otorhi-
nolaryngology department for further dierential diagnosis and biopsy.
Methods: e aim of this retrospective cohort study is to determine the
prevalence of iMCD in patients, who underwent a lymph node removal
in our clinic between 2010 and 2020. erefore, epidemiologic, laboratory
and clinical data was analysed descriptively while diagnosis of mono- and
multicentric M. Castleman disease were made utilizing the international
diagnostic criteria proposed by Fajgenbaum et al (2017).
Result: 714 patients suering of cervical lymphadenopathy were included
into the study. In 75 patients matching the clinical criteria for the diag-
nosis of iMCD histopathologic samples were re-analysed by a histopa-
thologist. 14 cases (1,9%) matched the histopathological major criterion
dened by Fajgenbaum et al, 2 cases (0,3%) matched for both major and
minimum required minor criteria.
Discussion: e new criteria from Fajgenbaum et al. oer an objective
tool for the diagnosis of iMCD. Even if the histopathological major crite-
rion oen ts for the extirpated lymph nodes, ≥ 2 enlarged lymph node
stations and complementary minor criteria were oen missing for the
nal diagnosis.
Conclusion: In our population aer utilization of the new criteria 1,9%
of patients could be diagnosed with monocentric and 0,3% could be diag-
nosed with iMCD in contrast to 0,1% respectively beforehand. Although
incidence and prevalence of iMCD are low, clinicians should keep in mind
this dierential diagnosis as eective therapies are available.
Disclosure Statement: e authors declare no conict of interest.
418
Inuencing factors for routine implementation of shared
decision-making in oncology: process evaluation of a stepped
wedge cluster-randomized trial
Anja Lindig; Pola Hahlweg; Wiebke Frerichs; Hannah Cords;
Jördis Zill; Isabelle Scholl
1Institut und Poliklinik für Medizinische Psychologie, Universitätsklinikum
Hamburg-Eppendorf, Hamburg, Deutschland
Background: Shared decision-making (SDM) is highly relevant in oncol-
ogy but rarely implemented in routine care. e outcome evaluation of an
implementation program to foster SDM in routine cancer care1 did not
nd an eect on SDM implementation from patients’ view. e aim of
this study was to analyze inuencing factors on SDM implementation in
routine cancer care.
Methods: We conducted a qualitative process evaluation of a stepped
wedge SDM implementation trial. Data included interviews with clini-
cal stakeholders, eld notes of the study team and minutes of meetings
with clinical collaboration partners. Data were analyzed via inductive
and deductive qualitative content analysis on basis of the Consolidated
Framework for Implementation Research (CFIR)2.
Result: Transcripts of 107 interviews, 304 pages of eld notes and 125
pages of meeting minutes were analyzed. Major inuencing factors on
SDM implementation were found on all levels of the CFIR: a) four on
the individual level (e.g., perceived personal relevance, individual moti-
vation to change), b) eleven on the organizational level (e.g., leadership
engagement, resources), c) two on the level of the health care system (e.g.
culture of healthcare delivery), d) eight regarding characteristics of the
intervention (e.g., translation into clinical practice, relative advantage),
and e) three regarding the implementation process (e.g., integration into
existing structures). We found strong correlations between several inu-
encing factors within and between levels.
Discussion: is comprehensive process evaluation provides approaches
for the interpretation of the outcome evaluation of the SDM implemen-
tation study. Future studies should investigate which of these factors are
predictors for implementation success.
Conclusion: e identied inuencing factors can be used for planning,
conducting and evaluating future SDM implementation studies.
References:
1 Scholl* I, Hahlweg* P, Lindig A, et al. (2021) Implementation Science.
16(1):106.
2 Damschroder LJ, Aron DC, Keith RE, et al. (2009) Implementation Science.
4:50.
Disclosure Statement: e authors declare no conict of interest.
467
What’s its worth? “Likes” as surrogate marker for interest
indigital medical education
Judith Büntzel; Julia Felicitas Leni König; Rebecca Wurm-Kuczera
Georg- August-Universität, Universitätsmedizin, Klinik für Hämatologie und
Onkologie, Göttingen, Deutschland
Background: Instagram is a novel tool in medical education and “likes
are oen used as surrogate markers to measure interest. However, “likes
have not been validated so far. We launched an educational Instagram
account teaching hematology and oncology and compared the numbers
of “likes” with an independent survey measuring the interest among the
participating students.
Methods: e Instagram account “ilearnonco2021” was generated and
teaching material was uploaded twice a day. Students were invited to
subscribe via e-mail and online announcements. “Likes” per post were
assessed. Once the teaching module was concluded, we launched an eval-
uation assessing students’ interest in posts of the category “mnemonics
and “clinical diagnostics” (blood smear, CT images) on a ve-point Likert
scale. Mann-Whitney U Testing was used to compare “likes” to the results
of our survey.
Result: 49 of 124 students enrolled in the teaching module subscribed.
Overall, we garnered 0.02 likes per post and follower number. e highest
“likes per post and follower number” (LPF) were observed in the posting
categories “mnemonics” and “clinical diagnostics” with 0.034 and 0.037
LPF respectively, indicating an increased interest. We assessed the stu-
dents’ interest in a separate evaluation at the end of the teaching module.
Comparing trends in interest between the two tools- “LPF” and the sur-
vey results, Mann-Whitney U testing revealed no signicant dierence
between both tools, indicating similar trends in students’ interest.
Discussion: So far, “likes” have been used as tool in digital research as
surrogate marker for interest. To our knowledge, we are the rst trying to
evaluate, whether “likes” are a suitable tool to estimate trends in interest
in medical education.
Conclusion: “Likes per post and follower” are suitable to estimate trends
in interest. e observed trends should be validated with a second tool,
e.g. an independent survey to conrm the ndings.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts186
502
Genomic HLA homozygosity is frequent in esophago-gastric
adenocarcinoma and related to low immunogenicity
María García-Márquez1; Martin Thelen1; Eugen Bauer2; Jonas Lehmann1;
Diandra Keller3; Birgit Gathof2; Lukas Maas4; Julie George3;
Christiane Bruns1; Alexander Quaas5; Michael von Bergwelt-Baildon6;
Martin Peifer7; Hans Schlößer1
1Uniklinik Köln, Zentrum für Molekulare Medizin Köln, Klinik und Poliklinik für
Allgemein-, Viszeral-, Tumor- und Transplantationschirurgie, Köln, Deutschland
2Uniklinik Köln, Transfusionsmedizin, Köln, Deutschland
3Uniklinik Köln, Clinics Head and Neck Surgery, Department of Translational
Genomics, Köln, Deutschland
4Uniklinik Köln, Department of Translational Genomics, Köln, Deutschland
5Uniklinik Köln, Pathologie, Köln, Deutschland
6Ludwig Maximilians University, Department of Medicine III, München,
Deutschland
7Uniklinik Köln, Computational Cancer Genomics , Department of Translational
Genomics, Köln, Deutschland
Background: e HLA-genotype of a person denes the repertoire of
peptides that can be presented to T cells. We aimed to determine if HLA-I
homozygosity could translate in a smaller repertoire of tumour neoanti-
gens potentially predisposing such individuals with a disadvantage to ght
a nascent tumour.
Methods: High-resolution HLA-genotyping combined with (1) the 10
most important cancer testis antigens (CTAs) in EGA (n=80) and (2) non-
synonymous mutations called from WES data (n=38) was used to predict
high and moderate anity binders with the “Immune Epitope Data Base
(iedb.org). RNA-extraction and gene expression proling were performed
using NanoString technology.
Result: Frequency of HLA homozygosity in EGA patients (n=80, 35%)
was unexpectedly higher than that in the control population (n=7.615,
19%). Comparison of both cohorts revealed an odds ratio for homozy-
gosity of at least one allele of 2.28 (p<0.001). Analysis of the amount of
tumour-specic high and moderate-anity binders conrmed a reduced
repertoire of potentially immunogenic peptides in homozygous EGA
patients. In line with this observation, increased levels of CTA expression
in homozygous compared to heterozygous patients were found. Aer
articial modication of the genotype of homozygous patients to a het-
erozygous genotype, the set of predicted good-binding peptides was com-
parable to the heterozygous cohort.
Discussion: Our results show a high frequency of HLA-I homozygos-
ity among EGA patients compared to healthy donors. Additionally, we
show that dierences in the number of available HLA-I molecules in a
given individual can present major challenges to eective antitumor T cell
responses that may facilitate immune evasion and may reect an increased
cancer risk for these patients.
Conclusion: Together with previous reports demonstrating reduced
survival aer checkpoint therapy, our study suggests consideration of
germ-line HLA-homozygosity for the design and interpretation of immu-
notherapeutic trials.
Disclosure Statement: e authors declare the following:
MvBB: Honoraria for advisory boards, for invited talks from BMS and nancial
support for research projects from Astellas, Roche and MSD; H.S.: Funding for
clinical Research by Astra Zeneca. Honoraria for advisory board from BMS; e
remaining authors declare no competing nancial interests
519
Structural and processual characteristics of multidisciplinary
tumor conferences from the physicians’ perspective
Kerstin Hermes-Moll1; Ulrike Mönnigho1; Thomas Walawgo1;
Vitali Heidt1; Jochen Heymanns2; Mathias Bertram3
1Wissenschaftliches Institut der Niedergelassenen Hämatologen und
Onkologen (WINHO) GmbH, Köln, Deutschland,
2Praxis für Hämatologie und Onkologie, Koblenz, Deutschland,
3Onkologie Partner, Praxis am Albertinen Krankenhaus, Hamburg, Deutschland
Background: Multidisciplinary tumor conferences (MTC) are an import-
ant and resource-intensive part of cancer care. Yet, there is a lack of knowl-
edge about structures and processes of MTC in Germany, esp. outside of
certied centers. Further, there is little information about potential quality
issues and measures to assure and improve the quality of MTC. is study
was supported by the Zentralinstitut für die kassenärztliche Versorgung in
der Bundesrepublik Deutschland (Zi).
Methods: An online survey was conducted from September 2021 until
January 2022. e questionnaire addressed structures, processes, and
quality of MTC. Physicians who treat cancer patients were invited to
participate via several professional organizations, e-mails, yers, social
media, and press. Data were collected anonymously and analyzed using
SPSS.
Result: Data from 612 respondents were included in the analysis.
Regarding the last MTC they attended, 83% stated that this MTC was
conducted by a certied center. MTC were held in presence in half of the
cases (51%), 30% in hybrid, and 19% purely virtual. e median value
for the duration of the MTC was 45-60 minutes, 11-15 for the number of
patients discussed, and 6-10 for the number of participants. However, the
range is large in each case. Concerning processual characteristics, signi-
cant dierences between MTC in certied and non-certied centers could
be identied, among others.
Discussion: e survey results show a great diversity regarding structural
characteristics of MTC. But there are also clear dierences with regard to
process-relevant factors, i.e. clearly dened guidelines and rules.
Conclusion: e results of this online survey provide a unique insight
into the landscape of MTC in Germany. Based on the results, critical
aspects and needs for further improvement of MTC can be identied and
addressed to optimize cancer care and time spent by physicians.
Disclosure Statement: e authors declare no conict of interest.
540
Patient seminars in oncology - online vs. presence: Has the
pandemic changed everything? Experiences after one year
of online events and results of a patient survey conducted by
CIO Cologne in July 2021
Sabine Treppner1
1Uniklinik Köln, Centrum für Integrierte Onkologie, Köln, Deutschland
Background: Aer the outbreak of the COVID-19 pandemic in spring
2020, it was no longer possible to hold face-to-face seminars with our
cancer patients. Nevertheless, there was an ongoing need for information
among the patients – in particular related to cancer and COVID-19.
Methods: Together with the patient representative from the board of our
cancer center, the Center for Integrated Oncology (CIO) at the University
Hospital Cologne, we discussed how a patient-oriented online format
could be designed. According to the principle “Monday is patient day”
a weekly, one-hour, moderated series of events was elaborated, for which
participants register only once and which alternates between entity-
specic and general topics like immunotherapy, nutrition, cancer and
sports. A key element of this new format was its interactive character
with very lively discussions. In additions, all events were available for the
patients as recordings.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 187
Result: A total of 41 events were held from August 2020 to July 2021. A total
of 1,298 people took part (max 95 /min 10) - this corresponds to an average
of 31.6 participants per event – with arising trend. e total of 32 recordings
have so far been accessed by a total of 1,598 people (max 140 / min 8) - this
corresponds to an average of 50 viewers per recording. (As of 8/30/2021)
Asked about their preference in the future, only 7% of 151 registered
online participants prefer a face-to-face event - 63% voted for online. 31%
would decide on a case-by-case basis.
Discussion: It was unclear, particularly among older oncology patients,
whether they would accept an online format well. ese concerns were
completely dispelled by both, the number of participants and the feed-
back from the survey. Compared to the face-to-face events before the
pandemic, participation was also signicantly increased through online.
Conclusion: e pandemic can be seen as a catalyst for a switch in infor-
mation sessions for oncology patients to online formats.
Disclosure Statement: e author declares no conict of interest.
609
Vascularsurgical aspects in oncosurgery of the retroperitoneal
space – representative case series
Frank Meyer1; Zuhir Halloul2
1Dept. of General, Abdominal, Vascular and Transplant Surgery, Otto-von-
Guericke University at Magdeburg with University Hospital, Magdeburg,
Deutschland,
2Division of Vascular Surgery, Dept. of General, Abdominal, Vascular and
Transplant Surgery, Otto-von-Guericke University at Magdeburg with University
Hospital, Magdeburg, Deutschland
Aim: Exemplary demonstration of vascular alterations incl. its recon-
structive options as part of retroperitoneal tumor(Tu) resections out of
the broad oncosurgical prole to achieve R0 resection status.
Method: Representative case reports showing technical feasibility & early
postop. outcome.
Results: 1) Preparative freeing of the Tu adherence of a retroperitoneal
so tissue sarcoma from the aorta near the sup. mesenteric artery (SMA)
& coeliac trunc incl. “le resection“ of the pancreas (+splenectomy, le
nephrectomy)/partial gastric/diaphragmatic resection (+thoracic drain-
age & suture of the intestine).
2) Multivisceral Tu resection of a retroperitoneal so tissue sarcoma, with
resection o he coeliac trunc & reconstruction of the hepatic artery using
venous interponate from the SMA.
3) Pancreatic head resection in a 45-year old patient with arterial supple-
mentation of the liver out of the SMA (hepatomesenteric trunc) only rec-
ognized aer ligation & surgical sectioning of the gastroduodenal artery
→ reconstruction with mesentericohepatic venous bypass.
4) Tu exstirpation of a right retroperitoneal neurinoma with adherence
to inferior vena cava, common iliac artery & psoas muscle w/o required
vascular reconstruction.
5) Tu resection of a primary inferior-vena-cava sarcoma comprising
vena-cava resection incl. the mouths of renal veins & reconstruction with
ringed PTFE prosthesis (Ø: 20 mm) reimplanting the renal veins.
6) Intraop. lesion of the SMA in Tu resection of a recurrent GIST at the
mesenteric root (intraperitoneal adhesions aer former peritonitis & sev-
eral laparotomies,recurrent liver metastases within segment 3, 4b, 5/8 &
ovarian tumor at both sides) reconstructed with venous patch plasty.
Conclusion: Vascular reconstructions partially necessary for a better
prognosis in interdisciplinary cases of abdominal & vascular surgery
require clinical & vascularsurgical expertise in reconstructions as well as
an interdisciplinary collaboration of interventional radiology & intensive
care in the perioperative management.
Disclosure Statement: e authors declare no conict of interest.
631
Technology acceptance of oncology patients with exercise
therapy needs to telemedicine-sports science services
Dominic Schmidt; Nora Zoth; Freerk T. Baumann
AG Onkologische Bewegungsmedizin, Uniklinik Köln, Centrum für Integrierte
Onkologie (CIO), Köln, Deutschland
Background: eHealth solutions promise great potential to provide can-
cer patients with individualized and scientically based exercise services
independent of time and location. ere is too little data on the accep-
tance of oncology patients for such products. erefore, this study investi-
gated cancer patients’ acceptance of telemedicine-sports science products.
Methods: 63 patients were shown a mock-up of a web browser por-
tal based on the concept of oncology exercise and movement therapy
(Onkologische Trainings- und Bewegungstherapie - OTT). ey then
completed an online questionnaire based on the technology acceptance
model. e acceptance of the respondents was measured by the item
"intention to use" (5-point Likert scale).
Result: e acceptance of the patients proved to be high. For the three
dierent functions of the product presented, the intention to use ranged
from 3.97 to 4.02. No age-related signicant dierences were found for the
mean scores (cut-o value 60 years).
Discussion: Overall, as suspected, a high level of acceptance was found.
Contrary to expectations, persons ≥ 60 years of age did not have a lower
expression in the item “Perceived ease of use”. e sample was small, so
this study is considered a pilot.
Conclusion: Probably, this online survey was thematically the rst of its
kind in Germany. It shows a positive attitude of the patients to the outlined
product. Further studies should follow. On the one hand, the question
arises as to which other variables inuence the intention to use (possibly
e.g., eHealth literacy or previous sports experience). On the other hand,
patients should be involved in the development of digital oerings from
the user perspective.
Disclosure Statement: e authors declare no conict of interest.
702
Mobile assessment of adverse events and other patient
reported outcomes (PROs) to guideinpatientcancer care:
athree-arm randomized controlled feasibility study
Hanna Salm1,2; Leopold Hentschel3; Michael Kramer4; Daniel Pink1,2;
Martin Eichler3,4; Markus K. Schuler4,5
1Department of Internal Medicine C, University Hospital Greifswald, Greifswald,
Deutschland
2Helios Hospital Bad Saarow, Bad Saarow, Deutschland
3University Cancer Center (NCT/UCC), University Hospital Carl Gustav Carus,
Technical University Dresden , Dresden, Deutschland
4Department of Internal Medicine I, University Hospital Carl Gustav Carus,
Technical University Dresden, Dresden, Deutschland
5Onkologischer Schwerpunkt am Oskar-Helene-Heim, Berlin, Deutschland
Background: e objectives of this study were to implement an electronic
assessment of patient reported outcomes (PROs) in inpatient cancer care
and test its feasibility. e eect of the mobile tool on symptom burden
and patients’ satisfaction with care was explored.
Methods: e study is an interventional, three-arm and multicenter inpa-
tient trial. A self-administered questionnaire consisting of several aspects
of quality of life using validated PRO-measures was applied and completed
at admission, one week aer and at discharge. Group A (intervention arm)
and B completed the questionnaires on a tablet computer, while group C
(control) completed the questionnaire on paper. Additional to the mere
of electronic patient reported outcome (ePRO) assessment, results from
group A were presented graphically to the treating physicians. A feasibility
questionnaire was administered to arm A and B.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts188
Result: N=185 patients were recruited in oncology wards. e majority
preferred the electronic version and believed the intervention had the
potential to improve care as well as had a positive impact on their treat-
ment. Unexpectedly, scores for satisfaction with care were signicantly
lower (p 0.047) in the intervention group (mean 3.55) versus the control
group (mean 3.77). Symptom burden did not signicantly change during
hospitalization.
Conclusion: ere is limited data available concerning ePRO assessment
in inpatient units. Our results indicate that the intervention is feasible.
We can therefore contribute to foster sustainable integration of ePRO in
the clinical routine. e results are counterintuitive but could possibly be
inuenced by missing physician compliance. ePRO success relies on the
investment of both sta and patients. Future work is needed to further
explore ePRO implementation in inpatient cancer care.
Disclosure Statement: e authors declare no conict of interest.
773
Inuence of the corona pandemic in exercise behavior,
quality of Life, anxiety and depression symptoms in adult
German cancer patients – an online survey:
Juliane Schenk1; Annika Klein1; Timo Niels2; Freerk Baumann2
1Institut für Kreislauorschung und Sportmedizin , Deutsche Sporthochschule
Köln, Köln, Deutschland
2CIO - Centrum für Integrierte Onkologie Uniklinik Köln, AG Onkologische
Bewegungsmedizin, Köln, Deutschland
Background: Covid-19 led to signicant restrictions in the daily life
for the German population. e aim of this study was to assess how the
corona pandemic impacted on physical activity (PA) behavior, quality of
life (QoL) as well as anxiety and depression symptoms of cancer patients.
Methods: Between May and July 2020, an online survey was conducted
for adult cancer patients in Germany, with access to organized exercise
programs. e questionnaire consisted of a cancer history, questions
about PA and exercise behavior before and during the pandemic, as
well as the standardized questionnaires EORTC C-30, HADS and FFKA
questionnaires.
Result: 117 subjects completed the survey. Exercise behavior was sig-
nicantly reduced during the pandemic compared to before (p = 0.004).
70.1% of the subjects stated that they are exercising less than before the
pandemic. With an average score of 58.12 within the global QoL scale,
patients met the matched reference values (61.4). e social function
scale achieved the lowest score (57,1. vs. reference data: 75,0) and physical
function the highest (74.2 vs. reference data: 76,7). On the symptomatic
scales, fatigue scale showed the highest symptom burden (48,24 vs. refer-
ence data: 34,6). 70.9% of the included patients stated that the restriction
of social contacts due to the pandemic had an impact on their QoL. e
mean HADS score was 10.62 points with 33.3% of the subjects exceeding
the cut-o value of ≥ 13.
Conclusion: PA decreased signicantly during the pandemic. QoL is
reduced compared to pre-pandemic EORTC reference data, with the
social function being most impaired. Regarding the development of
mental disorders, the sample can be classied as endangered. e use of
screenings for mental illnesses should be given greater consideration in
oncological care. Further studies are needed to assess the longer-term
impact of the corona pandemic on exercise behavior and psychosocial
eects in cancer patients.
Disclosure Statement: e authors declare no conict of interest.
816
Allocating resources in cancer care during pandemic.
Findings from a qualitative interview study with oncologists
and ethical analysis
Sabine Sommerlatte1; Anna-Lena Kraeft2; Celine Lugnier2; Eleni Kourti2;
Anke Reinacher-Schick2; Jan Schildmann1
1Institute for History and Ethics of Medicine, Martin Luther University Halle-
Wittenberg, Halle (Saale), Deutschland
2Department of Hematology, Oncology and Palliative Care, St. Josef-Hospital,
Ruhr University Bochum, Bochum, Deutschland
Background: Allocation of resources towards the treatment of patients
with Sars-CoV-2 may aect the quality of care of cancer patients. Medical
societies have issued statements on priority setting in cancer care in the
wake of the Sars-CoV-2 outbreak (1). However, there is a lack of empirical
data on how resources are prioritized and which criteria these decisions
are mainly based on by those involved in decision making.
Methods: 15 semi-structured interviews were conducted with oncologists
in Germany between February and July 2021. Transcripts are analysed
following principles of qualitative content analysis based on Kuckartz (2).
Result: According to preliminary analysis three main topics emerge: 1.
Experiences with scarcity regarding specic diagnostic procedures and
treatment 2. Eects of priority setting on coping and psycho-social sup-
port 3. Criteria for priority setting and decisions on deviations of stan-
dards of care. Reported criteria could be further distinguished into three
subcategories: a) criteria related to the health condition of the patient (e.g.
diagnosis, urgency of the procedure), b) pandemic-related organizational
issues (e.g. hygiene requirements), c) systemic aspects not related to the
pandemic (e.g. priorisation of well-paid interventions).
Discussion: Our data indicate that pandemic-related organizational issues
inuenced priority setting, which needs to be addressed. Furthermore,
interviewees agree in posteriorising palliative and follow up care, which
needs to be discussed regarding possible negative side eects.
Conclusion: Data will be interpreted focussing on the possible contribu-
tion to an informed guidance for priority setting regarding cancer care in
times of pandemic.
Indication of source:
1 Marron, JM et al. Ethics and Resource Scarcity: ASCO Recommendations for
the Oncology Community During the COVID-19 Pandemic. J Clin Oncol.
2020 Jul 1;38(19):2201-2205. doi:10.1200/JCO.20.00960.
2 Kuckartz, U. (2018). Qualitative Inhaltsanalyse. Methoden, Praxis, Computer-
unterstützung (4. Auage). Beltz Juventa.
Disclosure Statement: e authors declare no conict of interest.
835
Impact of the COVID-19 pandemic on cancer care services.
Qualitative interviews with health care users
Tugba Aksakal1; Yüce Yılmaz-Aslan1,2,3; Patrick Brzoska1
1Universität Witten/Herdecke, Fakultät für Gesundheit, Department für
Humanmedizin, Lehrstuhl für Versorgungsforschung, Witten, Deutschland
2Universität Bielefeld, Fakultät für Gesundheitswissenschaften, AG3
Epidemiologie und International Public Health, Bielefeld, Deutschland
3Universität Bielefeld, Fakultät für Gesundheitswissenschaften, AG6
Versorgungsforschung und Pegewissenschaft, Bielefeld, Deutschland
Background: Due to restrictions caused by COVID-19 and concerns
about contracting SARS-CoV-2, health care users avoided the health care
system, were less likely to have cancer screenings and delayed consulting a
doctor even if they had symptoms. As a result, more advanced cancers are
diagnosed, which are more dicult to treat. ere were also limitations in
ongoing cancer treatments. e aim of the study was to a) identify strate-
gies used in cancer care and prevention settings to mitigate the pandemic
and b) to assess the perceptions of these strategies by care users.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 189
Methods: In autumn 2021, 12 qualitative interviews were conducted with
health care users, including 8 cancer patients and 2 people each who did
or did not have screenings during the rst peak phase of the pandemic.
e interviews were analysed using content analysis.
Result: Reasons given by respondents for attending screening was a fam-
ily history of or having already survived cancer. Although they were con-
cerned about contracting SARS-CoV-2 during screening, they considered
the uncertainty about a potential cancer more worrying. Non-participants
cited concerns about infection and fear of a COVID-19 test as reasons for
non-participation, despite some having a family history of cancer. Cancer
patients perceived therapies carried out in isolation without relatives or
fellow patients as stressful. Compared to cancer, an infection with SARS-
CoV-2 was perceived as less threatening.
Discussion: Health care users and cancer patients, some of whom belong
to a risk group, are partly unaware of the risks associated with COVID-19
and missed cancer screenings. e low risk awareness was also reected in
the comparatively low vaccination rate of the sample, which could not be
attributed to medical reasons. Emotional support for cancer patients has
suered since the outbreak of the pandemic.
Conclusion: e risk awareness of health care users must be increased.
Psychosocial support for cancer patients must be ensured, especially in
times of crisis.
Disclosure Statement: e authors declare no conict of interest.
844
Caught in Speechlessness: First insights in patients with
oncology diseases
Thilo Dietz1; Vera Schiewer1; Sally Tavenrath1; Hildegard Labouvie1;
Michael Kusch1
1Klinik I für Innere Medizin, Universitätsklinikum Köln, Köln, Deutschland
Background: Speechlessness is a new and so far barely investigated eld
of research in psychology. e Cologne Questionnaire on Speechlessness
(KFS) [2] is the rst survey instrument that measures speechlessness
due to diculties in emotional perception and processing and identies
increased emotional speechlessness in individuals with a total sum score
of > 29 [1].
Methods: A total of N = 621 oncology patients were assessed for
speechlessness using the KFS; 75.5% of respondents provided complete
information.
Results: A total of n = 343 patients scored a total sum score > 29. Male
patients (n = 108) scored a signicantly lower total sum score (t(467)
= -2.592; p = .01; d = 17.9) and have a lower relative risk (RR = .84;
p = .028; 95% CI: .72 - .98) of suprathreshold speechlessness. Patients with
a diagnosis > 5 years (n = 141) scored signicantly lower (t(467) = 2.885;
p = .004; d = 17.87) than patients whose diagnosis was < 5 years (n =
328) and have a signicantly lower Releative Risk (RR = .85; p = .02; 95%
CI: .75 - .98) of suprathreshold speechlessness.
Discussion: Patients whose diagnosis and associated therapy (and bur-
den) occurred longer ago exhibit signicantly lower emotional speech-
lessness. It can be assumed that an oncological disease increases the
occurrence of emotional speechlessness.
Conclusions: Speechlessness in the context of oncologic disease should
be further explored.
Indication of source
1 Dietz et al. (2021). Kölner Fragebogen zur Sprachlosigkeit. Psychotherapeut.
https://doi.org/10.1007/s00278-021-00541-2
2 Dietz et al. (2022). Kölner Fragebogen zur Sprachlosigkeit: Entwicklung und
Validierung. Köln.
Disclosure Statement: e authors declare no conict of interest. e project was
nancially supported by the Barbara and Wilfried Mohr Foundation.
869
Treatment of immune thrombocytopenia (ITP) with
eltrombopag – results of the 5th interim analysis of the
German non-interventional trial RISA
Oliver Meyer1; Rudolf Schlag2; Thomas Stauch3; Bastian Fleischmann4;
Marcel Reiser5; Dietrich Kämpfe6; Timo Behlendorf7; Manfred Welslau8;
Eyck von der Heyde9; Steen Dörfel10; Claudia Willy11; Martina Stauch12
1DRK-Blutspendedienst NSTOB, Springe, Deutschland
2Hämatologisch-Onkologische Schwerpunktpraxis, Würzburg, Deutschland
3MEDIAN Reha-Zentrum, Bad Berka, Deutschland
4Cancer Center Dachau, Onkologisches Zentrum, Donauwörth, Deutschland
5PIOH Praxis Internistischer Onkologie und Hämatologie, Köln, Deutschland
6Praxis für Hämatologie und Onkologie, Lüdenscheid, Deutschland
7Gemeinschaftspraxis und Tagesklinik, Innere Medizin – Hämatologie –
Onkologie – Gastroenterologie – Palliativmedizin, Halle (Saale), Deutschland
8Onkologie Aschaenburg, Hämato-Onkologische Schwerpunktpraxis am
Klinikum Aschaenburg, Aschaenburg, Deutschland
9Onkologische Schwerpunktpraxis, Hannover, Deutschland
10Onkozentrum Dresden/Freiberg, Dresden, Deutschland
11Novartis Pharma GmbH, Nürnberg, Deutschland
12Ambulantes Zentrum für Hämatologie, Onkologie und Gerinnung, Kronach,
Deutschland
Background: Eltrombopag (EPAG) is a thrombopoietin-receptor agonist
approved for the second line treatment of ≥1 year old patients with pri-
mary immune thrombocytopenia (ITP) ≥6 months aer initial diagnosis.
Methods: RISA is a single-cohort, non-interventional, multicenter obser-
vational study, evaluating the treatment of ITP patients with EPAG. In
addition to hematological parameters, evaluation of fatigue, based on the
FACIT-F score, was part of the monthly examinations.
Result: Data cuto for this 5th interim analysis was 11.02.2022. 302
enrolled patients had at least one post-baseline visit. Median platelet
count increased from baseline 34.0x109/L (N=292) to 91.5x109/L (N=262)
and 108.0x109/L (N=146) within one month and 12 months, respectively.
Aer one month from baseline until the end of the observation period,
platelet counts remained stable above 90x109/L. e number of bleeding
events per patient-year decreased, from 1.35 at baseline to 0.59 aer one
year and to 0.16 aer two years. is corresponds to a reduction of yearly
bleeding events by 56% and 88% within the rst and second year, respec-
tively. At baseline, FACIT-F score indicated severe fatigue (N=233; mean
36.2; range 7–52). Aer 12 months, mean FACIT-F score was 38.5 (N=93;
range 1–52). In general, EPAG has been well tolerated. No new safety
signals were identied.
Discussion: Descriptive analyses suggested that EPAG therapy increased
the platelet count and reduced bleeding events, without any evidence of
new safety concerns. Fatigue is a signicant issue in patients with ITP, but
the eect of EPAG treatment on fatigue seems less pronounced than the
eect on platelet count and bleeding events.
Conclusion: EPAG is an eective and safe therapy for ITP. Within the
rst month of treatment, the platelet count increases and then remains
stable over a long period of time. Within two treatment years, the inci-
dence of bleeding events decreases by up to 88%. EPAG is less eective in
treating fatigue than in increasing platelet counts and reducing the risk
of bleeding.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts190
914
Use of patient versions of oncological clinical practice
guidelines in Germany - rst results of a qualitative study
Sarah Wahlen1; Jessica Breuing1; Monika Becker1; Stefanie Bühn1;
Nadja Könsgen1; Julia Hauprich1; Nora Meyer1; Susanne Bloedt2;
Ernst-Guenther Carl3; Markus Follmann4; Stefanie Frenz5; Thomas Langer4;
Monika Nothacker2; Corinna Schaefer6; Dawid Pieper7
1Institut für Forschung in der Operativen Medizin (IFOM), Universität Witten/
Herdecke, Köln, Deutschland
2Institut für Medizinisches Wissensmanagement, Arbeitsgemeinschaft der
Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) c/o Philipps-
Universität, Marburg, Deutschland
3Bundesverband Prostata Selbsthilfe e.V., Bonn, Deutschland
4Leitlinienprogramm Onkologie, Deutsche Krebsgesellschaft e.V, Berlin,
Deutschland
5Frauenhilfe Krebs Bundesverband e.V, Bonn, Deutschland
6Ärztliches Zentrum für Qualität in der Medizin (ÄZQ), Berlin, Deutschland
7Institut für Versorgungs- und Gesundheitssystemforschung und Zentrum
für Versorgungsforschung Brandenburg (ZVF-BB), Medizinische Hochschule
Brandenburg, Rüdersdorf bei Berlin, Deutschland
Background: Patients with cancer evolve information needs, which are
oen not fully addressed. Patient versions of clinical practice guidelines
(PVoGs) oer evidence based information in plain language. e purpose
of this study is to examine the use and dissemination of PVoGs from the
patients perspective in Germany.
Methods: Between September and November 2021, n=30 semi-struc-
tured telephone interviews with oncological patients were conducted.
Selected PVoGs were given to participants beforehand. e interviews
were analyzed with qualitative content analysis (Mayring) supported by
MAXQDA soware.
Result: e participants were predominantly female (60%) and 50% of the
participants had no awareness of the existence of PVoGs before participa-
tion. Aer reading the PVoGs all of the participants would recommend
them. e majority of participants consider the comprehensibility of
PVoGs to be good. According to the experiences of the participants, phy-
sicians hold an important role in information provision, but rarely refer
to or recommend PVoGs. ere are dierent opinions on PVoGs format
between patients. Some would prefer an app, while others would stick to
print or pdf. Age is stated by participants as a potential factor in the pref-
erence of format. An interactive use of the PVoGs is oen requested espe-
cially in the context of physician-patient communication, e.g. physicians
highlighting patient relevant details in text.
Discussion: Since physicians are essential to patients in information pro-
vision, the dissemination of PVoGs could be increased through active
handover within clinical appointments. Additionally, PVoGs could
improve patient-physician communication.
Conclusion: PVoGs are evidence-based patient information, which
are partially known by patients and poorly established in patient care.
Professionals could help to increase the dissemination and implementa-
tion of PVoGs in daily practice. Further research should investigate the
appropriateness of dierent formats of PVoGs.
Disclosure Statement: Some authors declare conict of interest.
1014
COVID-19 in cancer patients – higher inammatory response
in patients with active cancer
Maria Madeleine Rüthrich1,2,3; Yascha Khodamoradi4; Julia Lanznaster5;
Melanie Stecher6,7; Lukas Tometten8; Florian Voit9; Carolin E.M. Jakob6,7;
Stefan Borgmann10; Jörg Janne Vehreschild6,7,11; Bjoern-Erik Jensen12;
Frank Hanses13; Clemens Giessen-Jung14; Kai Wille15;
Marie von Lilienfeld-Toal3,16; Gernot Beutel17
1University Hospital Jena, Centre of Emergency Medicine, Jena, Deutschland
2University Hospital Jena, Institute of Medical Statistics, Computer and Data
Sciences, Jena, Deutschland
3Leibniz-Institut für Natursto-Forschung und Infektionsbiologie - Hans-Knöll-
Institut, Leibniz Institute for Natural Product Research and Infection Biology,
Jena, Deutschland
4University Hospital Frankfurt, Goethe University, Department of Internal
Medicine, Infectious Diseases, Frankfurt, Deutschland
5Passau Hospital, Department of Internal Medicine II, Passau, Deutschland
6University of Cologne, Faculty of Medicine and University Hospital Cologne,
Department I of Internal Medicine, Center for Integrated Oncology Aachen
Bonn Cologne Duesseldorf , Deutschland
7German Centre for Infection Research (DZIF), partner site Bonn-Cologne,
Cologne, Deutschland
8University Hospital of Cologne, Department I for Internal Medicine, Cologne,
Deutschland
9University Hospital Rechts der Isar, Technical University of Munich, School of
Medicine, Munich, Deutschland
10Ingolstadt Hospital, Department of Infectious Diseases and Infection Control,
Ingolstadt, Deutschland
11Goethe University, Department II of Internal Medicine, Hematology/Oncology,
Frankfurt am Main, Deutschland
12Heinrich Heine University, Department of Gastroenterology, Hepatology and
Infectious Diseases, Düsseldorf, Deutschland
13University Hospital Regensburg, Emergency Department, Regensburg,
Deutschland
14Ludwig Maximilian University, Department of Internal Medicine III, Munich,
Deutschland
15University of Bochum, University Clinic for Hematology, Oncology,
Hemostaseology and Palliative Care, Minden, Deutschland
16University Hospital Jena, Department of Internal Medicine II, Hematology and
Medical Oncology, Jena, Deutschland
17Hannover Medical School, , Department for Haematology, Haemostasis,
Oncology and Stem Cell Transplantation, Hannover, Deutschland
Background: Active cancer has been identied as an independent risk
factor for severity and mortality in COVID-19. However, direct compar-
isons of SARS-CoV-2 infected patients (pts) with active and non-active
cancers remain scarce.
Methods: We retrospectively analyzed a cohort of pts with cancer with
conrmed SARS-CoV-2 infection, enrolled 03/16/2020 – 07/31/2021.
Data on demographics, cancer and laboratory ndings were collected.
Descriptive and subsequent regression analysis was performed. Endpoints
were progression to severe COVID-19 and infection-associated mortality.
Result: In total, 987 pts with cancer (510 active vs 477 non-active) were
included in our analysis. Majority was male and > 55 years, with a higher
number of elderly pts with non-active cancer. CCI was 4.75 vs 3.85 in pts
with active and non-active cancer (p<0.001). Localized solid tumors were
reported in 38 vs 79% (p<0.001), metastasized in 37.5 vs 5.5% (p<0.001)
and hematological diseases in 37.5 vs 19.5% (p<0.001) pts with active and
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 191
non-active cancer, respectively. At virus detection, majority of pts showed
mild to moderate symptoms, while deterioration to severe COVID-19 was
slightly more common in pts with active cancer (19% vs 16%; p=0.284).
COVID-19 related mortality was signicantly higher in pts with active
cancer (24% vs 17.5%, p<0.001). In line, severe cytopenia and an increase
of inammatory markers were common ndings in pts with active cancer
at baseline, particularly in those who developed severe infection or died.
Multivariate analysis revealed that ferritin (14.24 [2.1–96], p=0.006) and
CRP (2.85 [1.02–8.02], p=0.046) were associated with severe COVID-19
and infection-related mortality. In pts with non-active cancer, association
was seen for ferritin only (4.1 [1.51–11.17], p=0.006).
Conclusion: Comparing pts with active and non-active cancer, mortality
rate was signicantly higher in pts with active cancer. Also inammatory
markers were signicantly increased assuming higher levels of inamma-
tion may play a role in adverse outcome of COVID-19 in pts with active
cancer.
Disclosure Statement: e authors declare no conict of interest.
1041
Seasonal community acquired respiratory viruses (CARV)
are associated with a high burden of disease in patients with
malignancies – preliminary data of the OncoReVir registry
Maria Madeleine Rüthrich1,2,3; Timo Schmitt4; Annika Y. Claßen5,6;
Michael von Bergwelt-Baildon7; Yascha Khodamoradi8;
Anna Dorottya Doleschall9,10; Larissa Henze11; Jena Panse9,10;
Gabriel Sauer8; Karsten Spiekermann7; Enrico Schalk12;
Maria Vehreschild8; Janne Jörg Vehreschild5,6,10,13; Daniel Teschner14;
Marie von Lilienfeld-Toal3,15; Nicola Giesen16
1University Hospital Jena , Centre of Emergency Medicine, , Jena, Deutschland
2University Hospital Jena, Institute of Medical Statistics, Computer and Data
Sciences, Jena, Deutschland
3Hans-Knöll Institute, Leibniz Institute for Natural Product Research and
Infection Biology, Jena, Deutschland
4University Medical Center of the Johannes Gutenberg-University, Department
of Hematology, Medical Oncology and Pneumology, Mainz, Deutschland
5University of Cologne, Faculty of Medicine and University Hospital Cologne,
Department I for Internal Medicine, Cologne, Deutschland
6German Centre for Infection Research (DZIF), partner site Bonn-Cologne,
Cologne, Deutschland
7University Hospital, Ludwig Maximilian University (LMU) Munich, Department
of Internal Medicine III, Munich, Deutschland
8Universitay Hospital Frankfurt, Goethe University, Department of Internal
Medicine, Infectious Diseases, Frankfurt am Main, Deutschland
9University Hospital RWTH Aachen, Department of Hematology, Oncology,
Hemostaseology and Stem Cell Transplantation, Aachen, Deutschland
10Center for Integrated Oncology (CIO), Aachen, Bonn, Cologne, Düsseldorf
(ABCD), Deutschland
11Rostock University Medical Center, Department of Medicine, Clinic III –
Hematology, Oncology, Palliative Medicine , Rostock, Deutschland
12Otto-von-Guericke University Magdeburg, Department of Haematology and
Oncology, Medical Centre, Magdeburg, Deutschland
13University Hospital Frankfurt, Goethe University, Department II of Internal
Medicine, Hematology/Oncology, Frankfurt, Deutschland
14Department of Internal Medicine II, University Hospital Würzburg, Würzburg,
Deutschland
15University Hospital Jena, Department of Internal Medicine II, Hematology and
Medical Oncology, Jena, Deutschland
16University Hospital Heidelberg, Department of Haematology and Oncology,
Internal Medicine V, Heidelberg, Deutschland
Background: Community acquired respiratory viruses (CARVs) may
cause severe respiratory infections in patients (pts) with cancer.To col-
lect epidemiological and clinical data of CARV-infections the multicentric
registry OncoReVir was established. Here, we present a preliminary anal-
ysis of pts with cancer infected with CARVs.
Methods: A total of 1,142 pts with cancer and CARV-infection were
enrolled betweenNov2018andJan2022. Most cases were documented for
season 17/18 and 18/19. Data on demographics, comorbidities, cancer,
CARVs and infection course were collected. Pre-dened endpoints were
pneumonia, admission to ICU and mortality. e relationship between
cancer-specic factors and outcome was evaluated by bivariate logistic
regression.
Result: e median age was 60 (IQR 50–67) years, 42% of pts were female.
Solid tumors were present in < 10%, leukemia, lymphoma and multiple
myeloma in 36.5%, 27% and 23%, respectively. 50% had active cancer, 40%
had received chemotherapy within the last 3 months. Targeted therapy
was reported in 11.5%, high-dose steroids in 16% of pts, 56% were SCT-
recipients. Commonly detected CARVs were inuenza (39.5%), parainu-
enza (18%), respiratory syncytial virus (15%), rhinovirus (14.5%), human
metapneumovirus (hMPV, 5.5%), endemic coronavirus (5.5%) and SARS-
CoV-2 (2%). Among all CARVs, frequent symptoms were cough, fever,
dyspnea and rhinitis. Rates of pneumonia were highest in hMPV (33%)
and SARS-CoV-2 (32%), lowest in endemic coronavirus (16%, p=0.334).
8.5% required intensive care, most of them due to COVID-19 (p=0.084).
Infection-associated mortality but not rate of pneumonia showed signif-
icant dierences comparing CARVs. In regression analysis, active cancer
was associated with all endpoints: infection-related mortality (4.02 [1.63–
9.88], p=0.002), ICU admission (1.75 [1.07–2.88], p= 0.027) and pneumo-
nia (1.47 [1.1–1.96], 0.009).
Conclusion: In our cohort, all CARVs could potentially lead to severe
disease. Active cancer was an independent risk factor for adverse outcome
in pts with cancer and CARV-infection.
Disclosure Statement: e authors declare no conict of interest.
1061
Pathogenic germline variants in BRCA and pregnancy
rates – data from a German Center of Hereditary Breast
and Ovarian Cancer
Susan Friedrich1,2; Dorothee Speiser1,2
1Charité - Universitätsmedizin Berlin, Klinik für Gynäkologie und
Geburtsmedizin, Berlin, Deutschland
2Charité - Universitätsmedizin Berlin, Zentrum Familiärer Brust- und
Eierstockkrebs, Berlin, Deutschland
Purpose: Women with pathogenic germline variants in BRCA1/2
presumably have a lower ovarian reserve.1
An overview of reproduction-associated problems of BRCA mutation
carriers (MC) compared to women without a pathogenic genetic variant
(PV) helps to counsel women with PV in fullling their desire to have
children in the future.
Methods: e study cohort included women with pathogenic germline
variants in BRCA detected at the Charité Center of Hereditary Breast and
Ovarian Cancer. Counselees and patients who have been tested nega-
tive before served as control group. Pregnancy rates and outcomes were
recorded through a questionnaire.
Results: 229 women were included in the study. e study population
consisted of 166 (72%) BRCA MC (between 18 and 80 years old). e
control population consisted of 63 (28%) women without a PV. e pro-
portion of nulligravida was 30.5% in the BRCA-subset and 22.6% in the
control group (p=0.55). Among BRCA MC, women reported 1.13, in the
control group 1.26 (p=0.40) live births. 6% of the BRCA-carriers needed
reproductive assistance in contrast to 1.6% of the control group (p=0.17).
e average age for 1st birth in BRCA MC is 28.5 years and without PV it
is 27.3 years (p=0.18).
Conclusions: e results support studies that have already indicated
lower ovarian reserve in BRCA MC, due to lower AMH-levels.2 Although
no signicant dierence in the number of nulligravidae or the number
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts192
of reproductive assistance could be established in our study, there was a
trend that women with PVs in BRCA seemed to have more diculties get-
ting pregnant. Larger cohort studies throughout Germany could conrm
this eect in the future.
(1) Oktay, Kutluk et al. “Association of BRCA1 mutations with occult pri-
mary ovarian insuciency: a possible explanation for the link between
infertility and breast/ovarian cancer risks.”Journal of clinical oncology
vol. 28,2 (2010): 240-4.
(2) Gasparri, Maria Luisa et al. “Ovarian reserve of women with and
without BRCA pathogenic variants: A systematic review and
meta-analysis.”Breast)vol. 60 (2021): 155-162.
Disclosure Statement: e authors declare no conict of interest.
1067
Qualitative methods for the evaluation of counseling sessions
in oncology
Jasmin Bossert1; Bianca Korus1; Helena Dürsch1; Ursula Boltenhagen2;
Mette Stie3,4; Nadja Klafke1
1Universitätsklinikum Heidelberg, Abteilung Allgemeinmedizin und
Versorgungsforschung, Heidelberg, Deutschland
2Universitätsklinikum Tübingen, Institut für Gesundheitswissenschaften und
Pegewissenschaften, Tübingen, Deutschland
3Lillebaelt Hospital, University Hospital of Southern Denmark, Department of
Oncology, Middelfart, Dänemark
4University of Southern Denmark, Department of Regional Health Research,
Faculty of Health Sciences, Odense, Dänemark
Background: Qualitative evaluation of oncology consultations is an
opportunity to gain insight into the communication between healthcare
providers and patients in order to give them the opportunity to actively
participate in their treatment. erefore, the aim of this scoping review is
to provide an overview of existing qualitative evaluation methods used in
the context of monoprofessional as well as interprofessional consultations.
Methods: We included all study types reporting on qualitative methods,
including mixed-methods studies, to analyse patient-provider consulta-
tions which were published from 1990 - 2020. We required databases to
identify relevant articles. Quality assessment was performed by the JBI
checklist for Qualitative Research.
Result: A total of 67 studies were included in this review (64 monoprofes-
sional, 3 interprofessional consultations). e most common counselling
context was treatment management, and oncological patients were most
frequently counselled. A total of 86 dierent qualitative analysis meth-
ods were identied, while content analysis was the most commonly used
method. One advantage of this method is the step-by-step procedure
using previously explained techniques. A disadvantage of the method
is that non-verbal aspects are not considered. Other possibilities for the
qualitative analysis of consultations are represented by grounded theory
and conversation analysis.
Discussion: Patient-centred communication is important in cases of seri-
ous illness. Integrating the analysis of patient-provider consultations is
one way to strengthen the latter. Qualitative methods which can be used
for analysis all oer advantages and disadvantages. Researchers should be
aware of these and weigh which method is best for their purposes.
Conclusion: is scoping review highlights dierent techniques for eval-
uating consultations and is intended to be a guide for other researchers
studying patient-provider communication to strengthen patient-centred
communication.
Disclosure Statement: e authors declare no conict of interest.
1068
Impact of the COVID-19 pandemic on GP care: Results
of a national survey in Germany
Tugba Aksakal1; Yüce Yılmaz-Aslan1,2,3; Patrick Brzoska1
1Universität Witten/Herdecke, Fakultät für Gesundheit, Department für
Humanmedizin, Lehrstuhl für Versorgungsforschung, Witten, Deutschland
2Universität Bielefeld, Fakultät für Gesundheitswissenschaften, AG3
Epidemiologie und International Public Health, Bielefeld, Deutschland
3Universität Bielefeld, Fakultät für Gesundheitswissenschaften, AG6
Versorgungsforschung und Pegewissenschaft, Bielefeld, Deutschland
Background: GP practices in Germany are facing many challenges due
to the COVID 19 pandemic. In addition to the general care of patients,
infection control measures and obligations in existing testing and vacci-
nation strategies led to an increased workload. e aim of this cross-sec-
tional study was to assess the ongoing and new workload related to the
pandemic, such as additional burden caused by booster vaccinations.
Furthermore, restrictions, e.g., on GP cancer screening and treatment,
were examined.
Methods: In December 2021 and January 2022, general practitioners
in Germany were invited to participate in a nationwide online survey
(n=3,050). e questionnaire was used to assess the impact of the pan-
demic on GP care. Responses were received from a total of 314 GP prac-
tices. Results were analysed descriptively.
Result: Challenges, restrictions and burdens resulting from the pan-
demic were still prevalent in GP practices at the time of the survey. e
additional need for the education of patients unwilling to get vaccinated
because of misinformation, as well as the diculties in the vaccination
campaign, e.g. delivery problems, were considered problematic. Including
vaccinations into work processes or impatience and lack of understanding
on the part of the patients were seen as particularly burdensome. GPs also
perceived a negative impact on cancer prevention and treatment.
Discussion: Adequate patient education can contribute to reducing mis-
information and thereby easing the workload in GP practices. Practical
guidelines can help to ensure adequate health care even in times of crisis
and also to protect particularly vulnerable patients.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 193
Paediatric Cancer
Best-of-Abstract-Vortrag
737
Medulloblastoma with extensive nodularity mimics cerebellar
development and dierentiates along the granular precursor
lineage
David Ghasemi1; Konstantin Okonechnikov2; Stephan Tirier3;
Anne Rademacher3; Jan-Philipp Mallm4; Kati Ernst5; Karsten Rippe4;
Stefan Pster1; Andrey Korshunov6; Kristian Pajtler1
1Hopp-Children’s Cancer Center Heidelberg (KiTZ), Heidelberg, Germany,
Division of Pediatric Neuro-oncology, German Cancer Consortium (DKTK),
German Cancer Research Center (DKFZ), Heidelberg, Germany, Department
of Pediatric Oncology, Hematology, and Immunology, University Hospital
Heidelberg, Heidelberg, Germany, Heidelberg, Deutschland
2Hopp-Children’s Cancer Center Heidelberg (KiTZ), Heidelberg, Germany,
Division of Pediatric Neuro-oncology, German Cancer Consortium (DKTK),
German Cancer Research Center (DKFZ), Heidelberg, Germany, Heidelberg,
Deutschland
3Division of Chromatin Networks, German Cancer Research Center (DKFZ) and
Bioquant, Heidelberg, Germany, Heidelberg, Deutschland
4Division of Chromatin Networks, German Cancer Research Center (DKFZ) and
Bioquant, Heidelberg, Germany, Single-cell Open Lab, German Cancer Research
Center (DKFZ), Heidelberg, Germany, Heidelberg, Deutschland
5Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ),
Heidelberg, Germany, Heidelberg, Deutschland
6Hopp-Children’s Cancer Center Heidelberg (KiTZ), Heidelberg, Germany,
Department of Neuropathology, Institute of Pathology, Heidelberg University
Hospital, Heidelberg, Germany, Heidelberg, Deutschland
Background: Medulloblastoma with extensive nodularity (MB/ MBEN)
represents a rare entity of cerebellar tumours of infancy comprising two
histologically distinct components that dier in cell dierentiation and
mitotic activity. While some children suering from MBEN experience
disease recurrence, MBEN can also dierentiate into benign tumours.
e underlying mechanisms of this variable biological behaviour remain
poorly understood but may oer insight into how cerebellar tumours of
infancy develop.
Methods: Fresh frozen tissue of nine MBEN-patients was subjected to a
multi-omics approach including bulk sequencing, microdissection, sin-
gle nucleus RNA-sequencing using the 10X Genomics- and SMART Seq.
V2-protocols and spatial transcriptomics via the RNAscope-platform.
Result: All cases were classied as Sonic Hedgehog (SHH)-MB, and har-
boured somatic mutations within the SHH-pathway. Aer quality control,
~30.000 cells were subjected to downstream analysis. Several non-ma-
lignant cell types, such as glial cells, were identied. In accordance with
previous studies, we found only sparse immune inltration. Based on
unsupervised clustering, we identied clusters of MBEN-cells that dif-
fered strongly in dierentiation state and represented a continuum from
embryonal-like cells with SHH-upregulation over intermediate cell states,
to neuronal-like, postmitotic cells. ese tumour cells reected stages of
normally developing cerebellar granular precursors. Using spatial tran-
scriptomics, we were able to correlate dierent clusters of MBEN cells
with MBEN’s two histologic compartments.
Discussion: While our results suggest that MBEN mimics physiological
embryonal development, the exact mechanisms behind this biological
behavior remain to be unraveled.
Conclusion: MBEN tumors are formed by a continuum of heterogenic
malignant cells that dierentiate along the granular precursor lineage.
is dierentiation process is reected in the bicompartmental structure
of MBEN.
Disclosure Statement: e authors declare no conict of interest.
Poster
2
Feasibility and acceptance of an exercise program
for pediatric patients with advanced cancer - a pilot project
Ronja Beller; Gabriele Gauß; Dirk Reinhardt; Miriam Götte
Zentrum für Kinder- und Jugendmedizin, Kinderheilkunde III, Hämatologie/
Onkologie, West Deutsches Tumor Zentrum, Universitätsklinikum Essen, Essen,
Deutschland
Background: Growing evidence suggests benets of exercise programs in
pediatric oncology and, patients should have access to exercise programs
during all treatment phases including palliative care. is pilot analyzes
the feasibility of exercise programs oered during hospital and home-
based palliative care.
Methods: e exercise program consisted of individual, supervised and
resource-oriented interventions home based or inhospital at least once a
week in palliative care. It comprised training of i.e. strength, endurance,
coordination, and body awareness according to patients’ wishes and daily
condition. ree children (girl, 13yrs – sarcoma; boy, 7yrs – leukemia;
boy 12yrs – sarcoma) participated. Data collection of psychological and
physical endpoints was intended to be every 4-6 weeks.
Results: Adherence to planned exercise sessions was 73±9% in a par-
ticipation range of 3-18 weeks with 54% of interventions at home, 36%
inpatient and 11% outpatient. Patients accepted the oer until close to
their death (last intervention was 10±3 d before death). Mean duration of
interventions was 66±10 min. Longitudinal data could only be assessed
from one participant. Results indicate an increase of psychosocial health
although physical health score was low and still decreased. Isometric
handgrip strength decreased, whereas leg strength increased over time.
No adverse events have occurred in relation to exercise.
Discussion: Results indicate that exercise was safe, feasible, and well tol-
erated by patients. Although data collection was partially impossible, high
needs and acceptance of this program showed the importance of support-
ive exercise programs for young patients with advanced cancer.
Conclusion: e individually adapted exercise programs might serve as
a supportive tool to reduce overall burden. Childrens and parents needs
were respected. More research in this treatment phase is needed.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts194
201
Development of patient-derived xenograft (PDX) models from
high-risk childhood cancers for preclinical evaluation of novel
therapeutics
Dennis Gürgen1; Johannes H. Schulte2; Anton G. Henssen2,3,4; Angelika
Eggert2; Wolfgang Walther1,3,4; Jan Koster5; Louis F. Stancato6; Stefan
Pster7; Jens Homann1
1Experimental Pharmacology and Oncology Berlin Buch GmbH, Berlin,
Deutschland
2Department of Pediatrics, Charité University Clinic Berlin, Division of Oncology
and Hematology, Berlin, Deutschland
3Max-Delbrück-Center for Molecular Medicine (MDC), Berlin, Deutschland
4Experimental and Clinical Research Center (ECRC), Charité University Clinic
Berlin, Berlin, Deutschland
5Academic Medical Center (AMC), Department Oncogenetics, Amsterdam,
Niederlande
6Eli Lilly and Company, PEDS Hub, Indianapolis, USA
7German Cancer Research Center (DKFZ), Division of pediatric Neurooncology,
Heidelberg, Deutschland
Background: Neuroblastoma (NB) and sarcomas represent aggressive
pediatric malignancies with highly variable clinical outcomes of imme-
diate fatal progression or spontaneous regression. Pronounced rates of
relapse, fast evolving resistance against standard-of-care (SOC) therapies
and a high degree of mutational mobility and heterogeneity indicate the
need for more precise and molecular targeted therapies.
Methods: Within the framework of the European IMI2 ITCC-P4 project
(Grant Agreement No 116064), we established a cohort of 10 NB and 35
pediatric PDX models of Ewing, osteo- and rhabdomyosarcoma (RMS)
closely resembling the human tumor architecture and molecular prole.
Aer stable growth of PDX models for 3-4 initial subcutaneous trans-
planted in vivo passages in immunodecient NOG mice, all models were
screened for sensitivity to selected SOC drugs and representative targeted
therapies.
Result: Pathology of all PDX models was veried using HE and IHC
staining of FFPE tumor sections. PDX doubling times dramatically varied
between 4 days in aggressive, 8 days in intermediate and up to 21 days in
slowly growing tumors. Strong in vivo ecacy was observed with SOC
drugs topotecan, cisplatin+cyclophosphamide in NB and trofosphamide,
actinomycin D+vincristine in RMS PDX models, though concomitant
with more pronounced side eects, especially in the combination treat-
ment. Interestingly, novel targeted therapies achieved similar anti-tumor
activity accompanied with good in vivo tolerability. Extensive analysis of
primary biopsies and PDX tumors utilizing whole-exome sequencing will
complete molecular characterization enabling translation of our pre-clin-
ical results.
Conclusion: Our pediatric PDX cohort is a powerful tool for further e-
cacy evaluation of targeted therapies in comparison to SOC compounds.
In vivo ecacy data together with PDX specic molecular proles will
support accelerated development of promising treatment regimens for
high risk pediatric cancers opening new therapeutic options and valuable
benets for pediatric patients.
Disclosure Statement: e authors declare no conict of interest.
625
A physical activity program on cardiorespiratory tness in
children and adolescents following acute cancer treatment
(POWER): study protocol for a randomized controlled trial
Miriam Götte1; Sandra Goertz2; Corina S. Rueegg3; Lisa Maas2;
TimNiehues2; Wolfgang Lawrenz4; Dirk Reinhardt1; Nina Brauer2
1Universitätsklinikum Essen, Klinik für Kinderheilkunde 3, Hämatologie/
Onkologie, Essen, Deutschland
2Helios Klinikum Krefeld, Zentrum für Kinder- und Jugendmedizin, Abteilung für
päd. Hämatologie und Onkologie, Krefeld, Deutschland
3Oslo University Hospital, Oslo Centre for Biostatistics and Epidemiology (OCBE),
Oslo, Norwegen
4Helios Klinikum Krefeld, Zentrum für Kinder- und Jugendmedizin,
Kinderkardiologie, Krefeld, Deutschland
Background: Treatment of pediatric cancer is associated with reduced
physical activity and performance as well as an increased risk to develop
chronic health conditions. It has been shown that VO2peak is reduced
both during and aer childhood cancer treatment. Regular exercise may
play a major role to preserve cardiorespiratory tness and to mitigate
sequelae. Primary aim of the POWER-RCT is to evaluate the eective-
ness of a partially supervised 12-week physical activity program on car-
diorespiratory tness (VO2peak) in pediatric cancer patients who have
recently completed treatment. Secondary outcomes are muscular strength,
functional mobility, coordination, cognitive function, changes in blood
and echocardiography parameters, physical activity levels, health related
quality of life, and fatigue.
Methods: A total of n=56 pediatric cancer patients aged ≥7 and <23 years,
who are 6 weeks post cancer therapy will be recruited. Following baseline
assessments, patients are randomized 1:1 into an intervention (IG) and a
control group (CG). e IG receives a multimodal partially supervised
12-week exercise program consisting of individual and group training ses-
sions. Participants of both groups receive a brochure with recommended
exercises and daily physical activities as well as a tness tracker to measure
the minutes of moderate to vigorous physical activities. Cardiorespiratory
performance, other physical, psychological, cognitive, and immunological
parameters are investigated in both groups.
Results: e POWER trial will provide insight into the eectiveness of an
early-administered physical activity program for pediatric cancer patients.
It might be a simple way to prevent future long-term treatment eects and
improve the general health state of these children.
Discussion: If eective, the intervention content will be translationally
implemented in the care setting of children and adolescents with cancer.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 195
823
Barriers to childhood cancer care in Sub-Saharan Africa –
a multinational, population-based cohort study
Ole Stöter1; Nikolaus Mezger1; Tamara König1; Ima-Obong Ekanem2,3;
Girum Tessema Zingeta4; Mathewos Assefa3,5,6; Franck Gnahatin3,7;
Henry Wabinga3,8; Mamadou Kéïta9; Eva Johanna Kantelhardt1,10
1Institute of Medical Epidemiology, Biometrics and Informatics, Martin‐Luther‐
University Halle‐Wittenberg, Halle (Saale), Deutschland
2Department of Pathology, University of Calabar, Calabar, Nigeria
3The African Cancer Registry Network, INCTR African Registry Programme,
Oxford, Vereinigtes Königreich
4Oncology Department, Tikur Anbessa Specialized Hospital, School of Medicine,
Addis Ababa University, Addis Ababa, Äthiopien
5Radiotherapy Center, Tikur Anbessa Specialized Hospital, Addis Ababa,
Äthiopien
6Addis Ababa Cancer Registry, Addis Ababa, Äthiopien
7Registre des cancers d’Abidjan, Abidjan, Côte d’lvoire
8Kampala Cancer Registry, Makerere University School of Medicine, Kampala,
Uganda
9Service du Laboratoire d’Anatomie et Cytologie Pathologique, CHU du point G,
Bamako, Mali
10Department of Gynaecology, Martin‐Luther‐University Halle‐Wittenberg, Halle
(Saale), Deutschland
Purpose: e WHO Global Initiative for Childhood Cancer aims to reach
60% survival rate by 2030 worldwide. For improved outcomes in child-
hood cancer (CC), it is decisive to start treatment swily, yet uptake of CC
care in Sub-Saharan Africa (SSA) is oen low and delayed. We conducted
a study to provide a comprehensive overview of barriers to CC care in
real-world patients in the region.
Methods: Our questionnaire study covers nine population‐based cancer
registries in nine countries across all Sub-Saharan regions (East, South,
Central, and West). Per registry, random samples of 20 to 50 patients diag-
nosed with any childhood cancer (age 0-19) between 2017 and 2019 were
selected. Patients, or their main caretakers were interviewed and data on
modality-specic barriers to chemotherapy, radiotherapy, and surgery
were collected.
Results: A total of 225 CC cases were included. Median age was 5 years
and the majority of patients was male. Over 80% of all CC patients
reported receipt of any cancer-directed therapy (surgery, radiotherapy or
chemotherapy), the majority receiving chemotherapy. Concerning barri-
ers to care, the perceived bad health status and the fear of side eects and/
or consequences of the treatment modality were named most frequently
as problematic (surgery 77.6% and 77.5%; radiotherapy 80.6% and 78.0%;
chemotherapy 73.9% and 80.6%). e results diered by region. For
example, a (high) cost of treatment was frequently considered problem-
atic in Eastern, Western and Central Africa but not in Southern Africa.
Discussion: In SSA, the availability of diagnostic services and treatment
facilities is widely considered most crucial to improve cancer care and
hence survival. Our study indicates that the perceptions and beliefs of
families of CC patients concerning the disease and its treatment prove to
be as important.
Conclusion: Patient education initiatives and health professional train-
ings should increasingly address concerns of caretakers and inform about
circumstances of cancer treatment to improve uptake of care and thus
prognosis of CC patients.
Disclosure Statement: e authors declare no conict of interest.
829
Analysis of cell-free dna in the plasma of patients with
non-resectable, progressive or relapsed pediatric
malignancies
Kendra K. Maass1,2; Pitithat Puranachot3,4; Paulina S. Schad1;
Agnes M.E. Finster1; Barbara Jones2,5,6; Tatjana Wedig1,2;
Nathalie Schwarz1; Petra Fiesel5,7,8; Gnanaprakash Balasubramanian1,3;
Jochen Meyer7,9; Felix Sahm5,7,9; Stefanie Zimmermann10;
David T.W. Jones5,6,8; Benedikt Brors3,8; Stefan M. Pster1,2;
Kristian W. Pajtler1,2
1Hopp Childrens Cancer Center Heidelberg (KiTZ), Heidelberg, Germany,
Division of Pediatric Neurooncology, German Cancer Consortium (DKTK),
German Cancer Research Center (DKFZ), Heidelberg, Germany
2Department of Pediatric Oncology, Hematology, Immunology and
Pulmonology, University Hospital Heidelberg, Heidelberg, Germany
3Division of Applied Bioinformatics, German Cancer Research Center (DKFZ),
Heidelberg, Germany
4Faculty of Medicine and Public Health, HRH Princess Chulabhorn College of
Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand
5Hopp Childrens Cancer Center Heidelberg (KiTZ), Heidelberg, Germany
6Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ),
Heidelberg, Germany
7Department of Neuropathology, Institute of Pathology, Heidelberg University
Hospital, Heidelberg, Germany
8German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ),
Heidelberg, Germany
9Clinical Cooperation Unit Neuropathology, German Consortium for
Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ),
Heidelberg, Germany
10Department of Pediatric Hematology and Oncology, University Hospital
Frankfurt, Frankfurt, Germany
Cell-free DNA (cfDNA) released by tumor cells provides the opportunity
to improve diagnosis and treatment using minimally invasive approaches
to molecularly survey clinically informative biomarkers and ‘action-
able’ targets. e ‘Individualized erapy for Relapsed Malignancies in
Childhood’ (INFORM) registry aims to identify actionable therapeutic
targets on a personalized basis. Relapsed or refractory high-risk tumors as
well as selected rare entities, for which no further standard of care therapy
is available, are characterized by state-of-the-art next-generation sequenc-
ing (NGS) technologies. Our study aims at integrating liquid biopsies into
the diagnostic INFORM pipeline and pave the way for clinical translation
of these technologies.
CfDNA for various downstream analyses is derived from plasma sam-
ples and isolated according to optimized protocols. Depending on the
yield of cfDNA, data availability for the primary tumor, and tumor entity,
we have performed low-coverage whole-genome sequencing (lcWGS),
whole exome sequencing (WES) and targeted gene panel sequencing.
Results are being compared with data obtained from standard tumor
biopsies and normal control tissues following adjustment of established
bioinformatics pipelines to suit liquid biopsy-derived data.
Sensitivity and specicity of our approach is presented as a proof-of-
concept study to compare the performance of dierent NGS platforms and
their utility for analyzing cfDNA samples. We demonstrate robust tumor
detection by lcWGS (n=115), mutation tracking by targeted approaches
(n=74) and the advantages of the combinatorial use of various approaches
(n=64).
We have demonstrated the feasibility of liquid biopsy analyses in
advanced pediatric malignancies. We highlight the informative values of
the liquid biopsy methods applied in terms of tumor detection, assess-
ment of tumor heterogeneity, and identication of actionable targets. Our
study is expected to guide and accelerate the implementation of liquid
biopsies into prospective pediatric clinical trials.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts196
934
Care, care needs and wellbeing of individuals after cancer in
childhood or adolescence (VersKiK)
Ekaterina Aleshchenko1; Thorsten Langer2; Gabriele Calaminus3;
Katja Baust3; Enno Swart1; Claudia Spix4; Pietro Trocchi1; Mathias Voigt4;
Peter Ihle5; Jutta Küpper-Nybelen5; Christian Lüpkes6; Thorben Kloppe6;
Patrik Dröge7; Dirk Horenkamp-Sonntag8; Ursula Marschall9;
Melanie Klein10; Iris Meier8; Christian Apfelbacher1
1Otto-von-Guericke Universität, Medizinischen Fakultät, Institut für
Sozialmedizin und Gesundheitssystemforschung, Magdeburg, Deutschland
2Universität zu Lübeck, Klinik für Kinder- und Jugendmedizin, Abteilung für
Pädiatrische Onkologie und Hämatologie, Lübeck, Deutschland
3Rheinische Friedrich-Wilhelms-Universität Bonn, Zentrum für Kinderheilkunde,
Abteilung für Pädiatrische Onkologie und Hämatologie, Bonn, Deutschland
4Universitätsmedizin Mainz der Johannes Gutenberg-Universität Mainz, Institut
für Medizinische Biometrie, Epidemiologie und Informatik, Mainz, Deutschland
5Universität zu Köln, PMV forschungsgruppe, Köln, Deutschland
6OFFIS e.V., Oldenburg, Deutschland
7AOK-Bundesverband GbR, Berlin, Deutschland
8Techniker Krankenkasse, Hamburg, Deutschland
9BARMER, Berlin, Deutschland
10DAK Gesundheit Hamburg, Hamburg, Deutschland
Care, care needs and wellbeing of individuals aer cancer in childhood or
adolescence (VersKiK)
A relevant proportion of childhood cancer survivors suers from late
eects, caused by the cancer itself or its therapy. To enhance their well-
being, follow-up guidelines were developed both on national and inter-
national levels. However, implementation of current German follow-up
guidelines is challenging due to organisational reasons or limited consid-
eration of psychosocial needs of survivors.
e overarching aim of the study is to provide representative evidence
about late-eects and follow-up care as well as in-depth understanding of
the care needs of childhood cancer survivors. Further aims are to examine
the adherence to selected follow-up guidelines and to suggest improve-
ments to them.
e present mix-methods, non-interventional study will analyse
claims data from German statutory health insurance funds in combina-
tion with individually linked by independent trust-centre anonymous
data from the German Childhood Cancer Registry. Perceived needs of
survivors, their informal caregivers and health professionals involved will
be investigated through volunteer interviews and focus groups.
e suggested study design will provide comprehensive evidence about
late eects of childhood cancer based on the largest available set of unse-
lected health care data in Germany. e description of the physical and
psychological late eects for a selected group of cancer diagnoses will help
to identify potential limitations and, consequently, suggest improvements
to the existing follow-up guidelines. An additional insight into actual state
of follow-up care and needs of cancer survivors, their informal caregivers
and healthcare provider involved will lay the groundwork for an improve-
ment of existing follow-up guidelines and possibly lead to new additions.
Disclosure Statement: e authors declare no conict of interest.
1060
Study protocol: Eects of a low vs. moderate intense exercise
program on immune recovery during pediatric allo-HSCT
(ANIMAL)
Ronja Beller1; Gabriele Gauß1; Sabrina Bianca Bennstein2;
Carolina Chamorro-Vina3; Helmut Hanenberg1; Dirk Reinhardt1;
Miriam Götte1
1Zentrum für Kinder- und Jugendmedizin, Kinderheilkunde III, Westdeutsches
Tumor Zentrum, Universitätsklinikum Essen, Essen, Deutschland
2Institut für Transplantationsdiagnostik und Zelltherapeutika AG Uhrberg /
Natürliche Immunität, Universitätsklinik Düsseldorf, Düsseldorf
3Kids Cancer Care Foundation of Alberta, University of Calgary, Calgary, Kanada
Background: Pediatric cancer patients undergoing allogeneic
Hematopoietic Stem Cell Transplantation (allo-HSCT) are at high risk for
life-threatening infections and transplant-related complications. Clinical
outcome aer allo-HSCT is closely associated with immune reconstitu-
tion, i.e. natural killer (NK-) cell counts ~30 days aer transplantation. In
general, exercise increases NK-cells in healthy and patient populations. In
the allo-HSCT setting, exercise positively inuences tness and psycho-
logical parameters. is exploratory study will evaluate the eects of indi-
vidualized exercise programs on NK-cells (primary aim), other immune
reconstitution parameters, performance and psychological endpoints and
transplantation outcomes.
Methods: A total of n= 20 pediatric cancer patients ≥4 years old, treated
with allo-HSCT will be recruited. Following baseline assessments,
patients are randomized 1:1 into an experimental intervention group 1
(EG1) with moderate intense exercise training and an experimental inter-
vention group 2 (EG2) with low intensity exercise training. Both groups
participate in multimodal supervised exercise sessions for 3-5x/week for
20-40min each with dierent contents (animals represent dierent con-
tents) and therefore dierent training intensities. Aer discharge EG1
receives 1-2x/week training until day +100 aer allo-HSCT. Immune and
laboratory (e.g. NK- and innate lymphoid cell subsets, IL-6/-7/-15/-33)
as well as performance and psychological parameters and transplantation
outcomes will be assessed.
Results: e ANIMAL trial evaluates the inuence of dierent intense
exercise programs on innate immune system recovery for children and
adolescents undergoing allo-HSCT.
Discussion: is trial might show if exercise can be used as a support-
ive care option to inuence immune recovery and to reduce infections.
If benecial, exercise could serve as a low-cost strategy to reduce days of
hospitalization and overall burden of the treatment.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 197
Palliative Care
Best-of-Abstract-Vortrag
976
Eect of a communication skills training for physicians on
early communication about palliative care and end-of-life
issues in advanced cancer patients: A randomized-controlled
trial (PalliKOM)
Nele Harnischfeger1; Hilke M. Rath2; Hannah Brand3; Karl Haller4;
Nicola Rieder5,6; Bernd Alt-Epping5,6; Anne Letsch3; Peter Thuss-Patience4;
Aneta Schieferdecker1; Carsten Bokemeyer1; Corinna Bergelt2;
Karin Oechsle1
1Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland
2. Medizinische Klinik und Poliklinik, Palliativmedizin, Hamburg, Deutschland
2Universitätsklinikum Hamburg-Eppendorf, Institut und Poliklinik für
Medizinische Psychologie, Hamburg, Deutschland
3Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik für Innere Medizin
mit Schwerpunkt Hämatologie und Onkologie, Kiel, Deutschland
4Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Medizinische
Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie,
Berlin, Deutschland
5Universitätsmedizin Göttingen, Klinik für Palliativmedizin, Göttingen,
Deutschland
6Universitätsklinikum Heidelberg, Klinik für Palliativmedizin, Heidelberg,
Deutschland
Background: In advanced cancer care, a timely communication of issues
related to palliative care (PC) and the end of life (EoL) has several bene-
ts for patients and caregivers. Yet, physicians’ insecurities oen impede
timely addressing those issues. Hence, we developed a short interactive
communication skill training (CST: PalliKOM) aiming to strengthen phy-
sicians in early and adequate communication.
Methods: We evaluated the CST (2x 90 min.) within a randomized-con-
trolled trial (RCT) at ve sites in Germany. Internal or organ-specic
oncologists were randomized into intervention group (IG) and wait list
control group (CG). At two assessment points, they lead a videotaped
medical consultation with a simulated patient. e IG received the CST
in-between, the CG aerwards. e videotapes were rated by study sta
blinded to group membership. Primary outcome were the observed com-
munication skills addressing PC-related topics. Further self and externally
assessed data served as secondary outcomes. Univariate analyses of cova-
riance with baseline adjustment were carried out for analysis.
Result: 141 physicians (age: M(SD) = 32.7(6.3), 59.8% female) took
part in this RCT (nIG = 73, nCG = 68). e IG shows signicantly more
improvement in communication skills than the CG on 4 of 5 rating scales:
emotions and empathy” (F(1,134) = 6.47, p = .012, partial η² = .045),
opportunities and hope” (F(1,136) = 7.74, p = .006, partial η² = .054),
addressing the end of life” (F(1,135) = 5.64, p = .019, partial η² = .040)
and “explaining the concept of palliative care” (F(1,138) = 15.63, p < .001,
partial η² = .102). Most secondary outcomes also improved signicantly.
Discussion: is PalliKOM-CST has proven eective in multidimen-
sional outcome parameters. Small to medium eect sizes might be due to
too high initial values in some areas.
Conclusion: A future implementation of the PalliKOM-CST will enhance
early communication of PC and EoL issues and thereby improve advanced
cancer care. Sponsored by the German Cancer Aid (DKH).
Disclosure Statement: e authors declare no conict of interest.
1062
Screening versus multidimensional assessment of symptoms
and psychosocial distress in cancer patients from the time of
incurability – a randomized study of the APM network
Stefanie Solar1; Florian Lordick2; Anja Mehnert3; Karin Oechsle4;
Birgitt van Oorschot5; Michael Thomas6; Johannes Wieditz7;
Thomas Asendorf7; Bernd Alt-Epping1,8
1Universitätsmedizin Göttingen, Klinik für Palliativmedizin, Göttingen,
Deutschland
2Universitäres Krebszentrum Universitätsklinikum Leipzig (UCCL), Leipzig,
Deutschland
3Universitätsklinikum Leipzig, Abteilung für Medizinische Psychologie und
Medizinische Soziologie, Leipzig, Deutschland
4Universitätsklinikum Hamburg-Eppendorf, Zentrum für Onkologie, Hamburg,
Deutschland
5Universitätsklinikum Würzburg (UKW), Würzburg, Deutschland
6Universitätsklinikum Heidelberg, Thoraxklinik Heidelberg, Heidelberg,
Deutschland
7Universitätsmedizin Göttingen, Institut für Medizinische Statistik, Göttingen,
Deutschland
8Universitätsklinikum Heidelberg, Klinik für Palliativmedizin, Heidelberg,
Deutschland
Background: Previous symptom prevalence studies show a broad spec-
trum of symptoms of varying intensity in patients being just diagnosed
with incurable cancer. It is unclear, though, how physical symptoms and
psychosocial distress should be recorded in order to determine the indi-
vidual need for palliative care.
Methods: We performed a randomized controlled longitudinal cohort
study comparing two dierent strategies for detecting symptoms and needs
of patients with newly diagnosed incurable cancer, determining the eects
on the further course of the disease: a low-threshold repeated screening
using NCCN Distress ermometer and iPOS, versus a comprehensive,
multidimensional assessment using FACT-G and its entity-specic scales,
PHQ4, SCNS-34-SF, iPOS and NCCN Distress ermometer. Primary
study endpoint was the quality of life aer 6 months, as determined by the
same assessment tools. Secondary study endpoints were the amount of
hospital days and the utilization of palliative care, emergency structures,
and psychosocial support.
Result: 504 patients from 34 study centers of the APM study network were
recruited (233 female, 271 male; mean age 66.6 (29 to 90) years). 207 par-
ticipants did not complete the 6 months observation period. Final results
are currently being analyzed and will be presented.
Discussion: e study sheds light on how physical symptoms and psycho-
social distress are best recorded in order to provide individually tailored,
early palliative care, in a cohort of patients known to suer from a variable
symptom spectrum.
Conclusion: e study results will add to the implementation of a struc-
tured supportive approach to incurably aected patients, and to the avoid-
ance of overuse, underuse and misuse of care in this highly relevant and
resource-intensive medical eld.
Disclosure Statement: e authors declare the following:
e study was funded by Innovationsfonds
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts198
Poster
21
Prediction of the survival time of palliative penile cancer
patients using clinical and laboratory prognostic parameters
and tools
Desiree Louise Dräger; Woehl Maria; Julia Nolting; Sophie Groh;
TimBuchholz; Oliver Hakenberg
Klinik und Poliklinik für Urologie, Universitätsmedizin Rostock, Rostock
Purpose: Making a prognosis is a very challenging and ethically sensi-
tive topic. e clinical impression oen leads to misjudgments. In most
cases, the remaining lifetime is assessed too optimistically and thus over-
estimated by up to 5 times. e prognosis of metastatic penile cancer in
the presence of distant metastases with a 5-year survival of less than 5% is
poor. e aim of the study was to evaluate prognostic tools with clinical
and laboratory parameters as well as potentially new predictors for the
survival time in palliative penile cancer patients.
Material: As part of a prospective monocentric follow-up study on pal-
liative tumor patients (n=23), clinical and laboratory parameters were
recorded, which were correlated with the remaining lifetime using the
univariate and multivariate Cox regression.
Results: e inammation parameters leukocytes (p=0.001), CrP
(p=0.001), albumin (p<0.001) and IL-6 (p<0.001) are signicantly
associated with survival time. Cystatin-C (p=0.014) and LDH (p=0.70)
also correlate signicantly with lifetime. Prognostic tools (KPS (p=0.012),
ECOG (p=0.001), PPI (p<0.001), PaP-S (p=0.001), GPS (p<0.001)) pro-
vide just as precise information.
Discussion: Prognosis assessment is essential for medical and personal
decisions. Although forecast gauges make accurate predictions, they are
rarely used.
Conclusions: Leukocytes, CrP, LDH and albumin have established
themselves as predictors of prognosis. Cystatin-C is also associated with
increased mortality and has not yet been part of a prognostic tool, but
could represent a suitable alternative.
Disclosure Statement: e authors declare no conict of interest.
99
Virtuelle Realität in der Palliativmedizin
Anja Flier1, Nancy Kuhn-Friedrich1, Dagmar Rolo1, Wolfgang Schütte1
1Halle (Saale), Krankenhaus Martha-Maria Halle-Dölau, Innere Klinik 2/
Palliativstation, Halle (Saale), Deutschland
Background: Die Implementierung der virtuellen Realität im DKG- zer-
tizierten LKZ, in der Klinik für Palliativmedizin, zur Angstreduktion
und zur Beruhigung bei innerer Unruhe bei Patienten in palliativmediz-
inischer Behandlung wird vorgestellt. In einer retrospektiven Erhebung,
von 2018 bis 2020, wurden 50 Patienten mit einem Bronchialkarzinom im
Endstadium analysiert.
Methods: Um die subjektive Einstellung bei dem Symptom der inneren
Unruhe und Angst messen zu können wurde als Messinstrument die
numerische Analogskala (NAS = 0-keine, 1-leichte, 2-mittlere, 3-starke
Belastung) als Scoring-System verwendet. Die Erhebung erfolgte in zwei
Gruppen mit jeweils 25 Patienten. Beide Gruppen erhielten standardis-
ierte erapieoptionen inkl. Respectare, die 2. Gruppe erhielt zusätzlich
die VR-Brille.
Result: In Gruppe 1 betrug der Anteil, die eine Verbesserung durch
standardisierte Optionen erzielen konnte, 71 %, bei der 2. Gruppe, unter
kombinierter Verwendung der VR-Brille, 89 %. Eine Verbesserung
von 1 oder mehr Punktwerten (NAS) konnten 85 % mit Verwendung
VR erlangen, wobei in der zweiten standardisierten Gruppe lediglich 49
% eine Verbesserung von 1 oder mehr Punktwerten erzielen konnten.
Beide Gruppen gingen mit einer Gesamtheit von 55,5 Punktwerten in die
Analyse ein. Nach Beendigung konnte in der 1. Gruppe 29 Punktwerte
und in der 2. Gruppe 37 Punktwerte erhoben werden
Discussion: Dies lässt erkennen, dass die Gruppe mit VR-Brille, mit doch
18 Prozentpunkten eine höhere Einwirkung auf die Symptomlast zeigt,
als die Gruppe mit standardisierten Optionen. Jedoch scheint Respectare
einen nachhaltigeren Einuss auf die Symptomlast zu haben.
Conclusion: Schlussfolgernd ist zu sagen, dass die Kombination der stan-
dardisierten erapieoptionen, die Berührung in Form von Respectare
und dem Angebot der VR Brille einen positiven Einuss auf die
Symptomlast hat. Demnach zeigt sich, dass moderne Technik kombiniert
mit menschlicher Zuwendung und respektvoller Berührung ein Gewinn
für die Patienten sein kann.
Disclosure Statement: e authors declare no conict of interest.
134
Predicting unplanned hospital readmission in palliative
outpatients (PRePP) – study protocol of a longitudinal,
prospective study to identify family caregiver-related and
structural predictors
Leopold Hentschel1,2; André Wellesen3; Luisa Christin Krause4;
Maria von Havranek4; Veronika Greiner4; Christiane Neumann-Stern4;
Michael Kramer5; Beate Hornemann1; Martin Bornhäuser5,6;
Ulrich Schuler2; Katharina Schütte4
1Nationales Centrum für Tumorerkrankungen (NCT/UCC), Universitätsklinikum
Carl Gustav Carus, Psychoonkologischer Dienst, Dresden, Deutschland
2Universitäts PalliativCentrum, Universitätsklinikum Carl Gustav Carus, Dresden,
Deutschland
3Nationales Centrum für Tumorerkrankungen (NCT/UCC), Universitätsklinikum
Carl Gustav Carus, Core Unit Patient-Reported Outcomes, Dresden, Deutschland
4Universitäts PalliativCentrum, Universitätsklinikum Carl Gustav Carus,
Spezialisierte Ambulante Palliativversorgung, Dresden, Deutschland
5Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus,
Dresden, Deutschland
6Nationales Centrum für Tumorerkrankungen (NCT/UCC), Universitätsklinikum
Carl Gustav Carus, Dresden, Deutschland
Background: Specialized outpatient palliative care aims to provide su-
cient end-of-life care, thereby alleviating symptoms and enable incurably
ill patients to stay at home till death. 52% - 94% of Germans desire to die
at home 12008. Relatives of these deceased persons were interviewed by a
written survey. Results: Aer removing duplicates, 4967 questionnaires
were sent out, 3832 delivered, and 1378 completed, yielding a response
rate of 36.0%. Regarding the deceased, 93.8% wanted to die at home, 0.7%
in a hospital, 2.8% in palliative care, 2.4% in a nursing home, and 0.3%
elsewhere. e gures for the relatives were 80.7%, 4.3%, 7.5%, 7.1%, and
0.5%, respectively. Of the deceased 58.9% and of the relatives 59.1% had
their wish fullled. Logistic regression analysis revealed that living in a
rural municipality (adjusted odds ratio [aOR]: 1.88; 95% condence inter-
val [CI]: 1.02-3.43 while actual place of death was home in less than one
third 2be it at a hospital, in a nursing home or at home (with/or without
home care. Unplanned hospital admissions (UHAs) contribute to this dis-
cordance and occur due to various reasons. PRePP aims to explore the
impact of informal caregivers’ (ICs) burden and characteristic of profes-
sional support as predictors for UHAs.
Methods: Starting in 04/21, PRePP is a prospective, observational, lon-
gitudinal, single-arm study to identify structural and ICs related factors.
PRePP uses standardized measures to assess ICs’ quality of life, psycho-
logical distress, anxiety, depression (WHOQOL BREF, NCCN Distress
ermometer, GAD-7, PHQ-9). Furthermore, characteristics of profes-
sional support-network and symptoms are assessed.
Result: In 02/22 the recruitment of 250 patients (sex: 41% f, 59%m; age:
mean=73, SD=13.8) was completed. A preliminary, descriptive partial
analysis of T1 showed the following results: 61% had a participating IC
(sex: 78% f, 22% m; age: mean=65, SD=14.8). Results of the WHOQOL
suggest an average quality of life for ICs. However, ICs are most likely
to experience restrictions on this through negative aect and insucient
opportunities for leisure activities.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 199
Discussion: As this study applies an explorative mono-centric design,
its results will be of preliminary character. Based on the partial results,
we suspect an underrepresentation of highly burdened ICs as they might
refrain from participation.
Conclusions: PRePP supplements scarce knowledge in predicting UHAs
to develop clinical screening tools for UHAs.
References:
1. Escobar Pinzon, L. C. et al. Preference for place of death in Germany.
J. Palliat. Med. 14, 1097–1103 (2011).
2. Sauer, S., Müller, R. & Rothgang, H. Institutionalised dying in
Germany: Trends in place of death distribution: home, hospitals and
nursing homes. Z. Gerontol. Geriatr. 48, 169–175 (2015).
Disclosure Statement: e authors declare no conict of interest.
167
Digitalisierung am Lebensende: Potentiale und Akzeptanz
von Informations- und Kommunikationstechnologie in der
Palliativversorgung (DigiPall) - Zwischenergebnisse
Felix Muehlensiepen1; Anne Gehlhaar1; Felizitas Linderkamp1; Susann
May1; Dunja Bruch1; Kerstin Stahlhut2; Martin Heinze1,2
1Medizinische Hochschule Brandenburg Theodor Fontane, Neuruppin,
Deutschland
2Immanuel Klinik Rüdersdorf, Rüdersdorf bei Berlin, Deutschland
Background: Information and communication technologies (ICT) are
considered an opportunity to support palliative care (PC). e eective-
ness of ICT in PC delivery has only been demonstrated to a limited extent.
e aim of this study is to investigate the use of ICT in PC using a qualita-
tive study design and thus to create a theoretical basis for the development
of a research agenda.
Methods: To explore this domain, telephone-based guided interviews are
conducted with a heterogeneous sample health care practitioners (HCP)
in PC (n≈19). e interviews are analysed using Kuckartz’s structuring
content analysis, supported by MAXQDA.
Result: ICT is used to varying degrees in the dierent settings of PC.
Providers perceive the use of ICT as complementary. ICT enables the
support of work processes, which can relieve the providers’ time. ICT
supports and intensies communication between providers as well as
between providers and patients and their caregivers. In doing so, it reduces
information losses. ICT can increase the quality of care and strengthen
patient-centred care by connecting health care professions/institutions
respectively the use of diagnostic and therapeutic options. e use of ICT
can lead to security risks. Technical decits or insucient user competen-
cies can lead to ineciencies in the care process. ICT impairs communi-
cation, with the result that the multidimensionality of PC is not ensured
by exclusive ICT based care.
Discussion: In order to use ICT eectively in PC, the context factors
under which digital communication takes place and the acceptance of the
users, also including the perspective of patients and their relatives, require
in-depth investigation. Participatory research and development of ICT
might add signicant value to end-of-life care provision.
Conclusion: ICT is perceived by providers as an important support to PA
and is therefore used in many ways. ICT can complement, but not replace,
direct physical contact with patients and their families.
Disclosure Statement: e authors declare no conict of interest.
497
Eect of early palliative care on the distress of oncological
patients with high symptomatic burden, a prospective pilot
study
Anja Thronicke1,2; Philipp von Trott3; Friedemann Schad1,3
1Forschungsinstitut Havelhöhe gGmbH am Gemeinschaftskrankenhaus
Havelhöhe, Berlin, Deutschland , Berlin, Deutschland
2Institut für Sozialmedizin, Epidemiologie und Gesundheitsökonomie, Charité–
Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and
Humboldt-Universität zu Berlin, Berlin, Deutschland
3Interdisziplinäre Onkologie und Palliativmedizin, Gemeinschaftskrankenhaus
Havelhöhe, Berlin, Deutschland
Background: Oncological patients with high symptomatic burden suer
from psychological and physiological constraints during end-of-life care.
Early palliative care (ePC) has been shown to signicantly improve the
quality of life of oncological patients and may lead to longer survival (1).
e objective of this study is to compare the distress of high symptomatic
burdened oncological patients before and aer inpatient ePC.
Methods: 38 stage I-IV oncological patients with self-reporting of ≥ 5
points on the NCCN Distress ermometer scale (2) are included. e
primary endpoint is the improvement of self-reported distress by 2 points
(NCCN Distress ermometer) 12±2 days aer the start of ePC. e sec-
ondary endpoints are the evaluation of distress, symptom intensity, over-
all and progression free survival and complication rate. e applied ePC
consists of guideline-oriented symptom management, elaborate consul-
tation life review (3), complementary medication and non-pharmacolog-
ical applications. e statistical analyses will be performed descriptively.
Study’s registration number: DRKS00013335.
Result: 20 of 38 oncological patients have already been included in the
study. It is anticipated that patient’s distress as a measurement of anxiety
and depressive symptoms will improve 12±2 days aer the start of inpa-
tient ePC.
Discussion: First results will be shown and discussed.
Conclusions: It is expected that patients symptomatic burden will be
reduced by the application of ePC in the presented study. Meanwhile, a
multicenter study is being prepared and participating palliative care cen-
ters are invited.
Indication of source:
1 Temel JS et al. New England Journal of Medicine 2010
2 Mitchell AJ et al. J Clin Oncol 2017
3 ronicke A et al. Complement Med Res 2018
Disclosure Statement: FS reports grants from AstraZeneca, Abnoba GmbH,
Iscador AG, and Helixor Heilmittel GmbH outside the submitted work. e other
authors declare no conict of interest.
634
Dying in Hospitals – Optimization of care in the dying phase
(StiK-OV) – Results of an online survey
Sukhvir Kaur1; Karin Oechsle2; Holger Schulz3; Kathleen Boström1;
Nikolas Oubaid2; Christina Plathe-Ignatz2; Anneke Ullrich2;
Raymond Voltz1; Kerstin Kremeike1
1University of Cologne, Faculty of Medicine and University Hospital Cologne,
Department of Palliative Medicine, Köln, Deutschland
2Palliative Care Unit, Department of Oncology, Hematology and BMT, University
Medical Center Hamburg-Eppendorf, Hamburg, Deutschland
3Department of Medical Psychology, University Hospital Hamburg-Eppendorf,
Hamburg, Deutschland
Background: Hospitals are the most frequent place of death in Germany
(47%), but at the same time, the least preferred one – for both patients and
their relatives. To optimize care in the dying phase by using a bottom-up
approach, the StiK-OV project aims to implement and evaluate specic
measures on dierent non-palliative wards at two university hospitals. In
the rst phase of the project, we assess the current state of care in the dying
phase on dierent wards.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts200
Methods: We conducted an online survey with national health care pro-
fessionals consisting of seven open questions on important aspects, facili-
tators, barriers and needs for improvement as well as Covid-19 pandemic
specics regarding care in the dying phase. Qualitative data was analyzed
thematically.
Result: Of 67 participants, 66% work in clinical practice as nursing sta
(52%) and physicians (30%) and 34% in management or administration.
As relevant topics of care in the dying phase, we identied involvement of
relatives, symptom control, patient-centeredness, professional competen-
cies, as well as time, space and human resources. Participants state a need
for improvement regarding these topics. During the pandemic, involve-
ment of relatives and patient-centeredness were dicult to maintain due
to visiting restrictions and higher workload, resulting in patient isolation
and dying in loneliness.
Discussion: e survey revealed common topics of importance which
should be targeted by ward-specic measures. Diculties due to the pan-
demic have to be accounted for to achieve optimal care in the dying phase
under exceptional circumstances.
Conclusion: e survey gave insights on care in the dying phase from
the perspective of health care professionals that can help to develop and
implement situation-specic measures to signicantly improve the quality
of care during the dying phase in hospitals. A bottom-up approach aims to
increase the sta motivation to implement respective measures.
Disclosure Statement: e authors declare no conict of interest.
855
Percutaneous Endoscopic Gastrostomy for palliative therapy
in oncological patients – the safety of a vulnerable cohort in a
large retrospective, monocentre Charité study
Tobias Kinzel1; Viktoria Reich1; Leonie Schuhmacher1; Christian Bojarski1;
Andreas Adler2; Wilfried Veltzke-Schlieker2; Christian Jürgensen2;
Bertram Wiedenmann2; Britta Siegmund1; Federica Branchi1;
Juliane Buchkremer1; Christoph Treese1
1Charité – Universitätsmedizin Berlin, corporate member of Freie Universität
Berlin and Humboldt-Universität zu Berlin, Department of Gastroenterology,
Infectious Diseases and Rheumatology (including Nutrition Medicine), Berlin,
Deutschland
2Charité – Universitätsmedizin Berlin, corporate member of Freie Universität
Berlin and Humboldt-Universität zu Berlin, Department of Hepatology and
Gastroenterology, Berlin, Germany, Berlin, Deutschland
Background: Especially oncological patients, whose conditions require
palliative care, are part of the daily ethical discussion in every clinic. e
benets of an intervention like the PEG-Insertion must be carefully eval-
uated. In this analysis, we focussed on the safety prole regarding the per-
formance status and the three dierent PEG-insertion techniques.
Methods: e cohort of patients in palliative care with an oncological
diagnosis is a subgroup based on a large retrospective database of patients,
receiving a new PEG between January 2016 and December 2021 in the
three endoscopic centers of the Charité-Universitätsmedizin Berlin. To
investigate the safety prole of PEG in this subgroup we did uni- and mul-
tivariate analyses.
Result: 146 patients with oncological diagnosis and PEG-insertion within
the context of palliative therapy were included and compared with 1424
patients. Neither the performance status (ECOG 1/2 und ECOG 3/4;
p=0.117) nor in comparison to the whole cohort (p=0.961) dierences
regarding major complications were evaluated. e gastropexy-tech-
niques (direct puncture and Hybrid) demonstrated its benet compared
to the pull-through method in the cohort with other diagnoses (p<0.001),
while the results in the subgroup just pointed out a tendency (Gastropexy
2.1; pull-through 9.8%).
Discussion: e study is mostly limited by its retrospective design and
especially the small number of patients with major complications in the
subgroup.
Conclusion: Despite the necessity of a strict following of the indications we
assume that PEG-insertion for palliative therapy in oncological patients is
as safe as it is for other cohorts and that the safety prole of the procedure
is independent of the performance status. Furthermore, our data suggest
even in this special cohort a benet for both gastropexy-techniques.
Disclosure Statement: e authors declare no conict of interest.
1023
Standardized screening for palliative care needs on elective
admission to in-patient oncological unit
Astrid Schnabel1; Kathrin Reetz2; Nicole Wegener3; Eva-Maria Balsen2;
Florian Lordick1; Sven Bercker3
1Universitätsklinikum Leipzig, Klinik und Poliklinik für Onkologie,
Gastroenterologie, Hepatologie, Pneumologie und Infektologie, Leipzig,
Deutschland
2Universitätsklinikum Leipzig, Klinik und Poliklinik für Onkologie,
Gastroenterologie, Hepatologie, Pneumologie und Infektologie,
Patientenmanagment, Leipzig, Deutschland
3Universitätsklinikum Leipzig, Klinik für Anästhesiologie und Intensivmedizin,
Leipzig, Deutschland
Standardized screening for palliative care needs on elective
admission to in-patient oncological unit
Background: While implementing the national cancer certication pro-
gram for oncological and comprehensive cancer centres we collected and
analysed data prospectively for quality assurance.
Methods: Screening was conducted pencil-paper-based using the vali-
dated new Minimal Documentation System (MIDOS²) and the Distress
ermometer (DT) for self-assessment for physical symptoms and psy-
chosocial distress of cancer patients. MIDOS² sum score >4 or a DT score
>4 was dened as positive for palliative care needs assessment. In these
cases, an automatic referral to the specialist in-patient palliative care ser-
vice was triggered. Subsequently, either specialist palliative care or coun-
selling for general palliative care was applied.
Results: In 2021, 139 cancer patients had been electively admitted to
our oncological unit. All but two of these patients underwent the above
screening process. e response rate was 91% (n=125). Out of these 125
cases, 65 patients (52%) were screened positive for palliative care needs
assessment. Of these, in 60 cases (92%) an automatic referral to the spe-
cialist in-patient palliative care service was triggered. Finally, in 35 cases
the palliative care needs assessment was performed. Out of these, 23 cases
(66%) received general palliative care counselling, and 12 cases (34%) spe-
cialist palliative care. Screening identied 9% of electively admitted cases
as in need for specialist palliative care.
Conclusion: It is possible to integrate a standardized screening for pal-
liative care needs on planned clinical routine admission to oncological
in-patient units. As such, this screening is able to complement the a priori
referral to specialist in-patient palliative care service, by that contributing
to comprehensive oncological care.
Disclosure Statement: e authors declare the following:
Vortragshonoraria DGK
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 201
Psychooncology
Best-of-Abstract-Vortrag
359
Distress in hospitalized cancer patients: Associations
with personality traits, clinical and psychosocial
characteristics
Theresia Pichler1; Birgitt Marten-Mittag2; Kerstin Hermelink3;
Eva Telzerow4; Tamara Frank1,2; Ulrike Ackermann5; Claus Belka6;
Stephanie E. Combs7,8,9; Christian Gratzke10,11; Jürgen Gschwend12;
Nadia Harbeck3,13; Volker Heinemann1,4; Kathleen Herkommer12;
Marion Kiechle5; Sven Mahner3; Ste Pigorsch14; Josene Rauch6;
Christian-Georg Stief11; Friederike Mumm1,4; Pia Heußner4,15;
Peter Herschbach2; Andreas Dinkel2
1Comprehensive Cancer Center Munich, Munich, Deutschland
2Technical University of Munich, School of Medicine, Klinikum rechts der
Isar, Department of Psychosomatic Medicine and Psychotherapy, Munich,
Deutschland
3Department of Obstetrics and Gynecology, University Hospital, LMU Munich,
Munich, Deutschland
4Department of Internal Medicine III, University Hospital, LMU Munich, Munich,
Deutschland
5Technical University of Munich, School of Medicine, Klinikum rechts der Isar,
Department of Gynaecology and Obstetrics, Munich, Deutschland
6Department of Radiation Oncology, University Hospital, LMU Munich, Munich,
Deutschland
7Helmholtz Zentrum München (HMGU), Department of Radiation Medicine,
Oberschleißheim, Deutschland
8Deutsches Konsortium für Translationale Krebsforschung (DKTZ), partner site
Munich, Deutschland
9Technical University of Munich, School of Medicine, Klinikum rechts der Isar,
Department of Radiation Oncology, Munich, Deutschland
10Department of Urology, University Hospital of Freiburg, Freiburg, Deutschland
11Department of Urology, University Hospital, LMU Munich, Munich,
Deutschland
12Technical University of Munich, School of Medicine, Klinikum rechts der Isar,
Department of Urology, Munich, Deutschland
13Breast Center, University Hospital, LMU Munich, Munich, Deutschland
14Technical University of Munich, School of Medicine, Klinikum rechts der Isar,
Department of Radiation Oncology, Munich, Deutschland
15Cancer Center Oberland, Garmisch-Partenkirchen General Hospital, Garmisch-
Partenkirchen, Deutschland
Background: Identication of psychosocial distress and associated deter-
minants is important for allocation and supply of patient-oriented psy-
cho-oncological support. is study investigated the associations between
dispositional characteristics and current clinical and psychosocial deter-
minants of distress in hospitalized cancer patients.
Methods: e cross-sectional study investigated 879 inpatients with dif-
ferent cancer sites treated in the Comprehensive Cancer Center Munich.
Assessment of determinants of elevated distress comprised sociodemo-
graphic, clinical and psychosocial characteristics as well as dimensions of
personality. We calculated a multiple linear regression to identify determi-
nants of psychosocial distress.
Result: Overall, 46.2% (n = 406) of the participants reported clinically
signicant distress. Results of the multiple linear regression model showed
that younger age, higher neuroticism, having metastases, being in a worse
physical condition, depressive symptoms, not feeling well informed about
psychological support and previous psychological treatment were signi-
cantly associated with higher psychosocial distress.
Discussion: Psychosocial distress of cancer patients is associated with
dispositional vulnerability, i.e. neuroticism, as well as current clinical and
psychosocial characteristics.
Conclusion: Health care professionals should consider both, the more
transient emotional responses, such as depressive symptoms, as well as
more enduring patient characteristics, like neuroticism.
Indication of source
Pichler T, Dinkel A, et al. Distress in hospitalized cancer patients:
Associations with personality traits, clinical and psychosocial characteris-
tics. Psychooncology. 2019;28(10):2049-59. (submitted)
Pichler T, Dinkel A, et al. Distress bei stationären Krebspatienten:
Zusammenhänge mit Persönlichkeitsmerkmalen, klinischen und psycho-
sozialen Determinanten. (submitted to 19. PSO-Jahrestagung)
Disclosure Statement: e authors declare no conict of interest.
871
Open the door for parental themes. The development and
evaluation of an intervention for healthcare professionals on
parenthood and cancer. A randomized controlled pilot-study
Lene Marie Johannsen1; Wiebke Frerichs1; Laura Inhestern1; Rebecca
Philipp1; Corinna Bergelt1,2
1Institut und Poliklinik für Medizinische Psychologie, Universitätsklinikum
Hamburg-Eppendorf, Hamburg, Deutschland
2Institut für Medizinische Psychologie, Universitätsmedizin Greifswald,
Greifswald, Deutschland
Cancer patients with minor children face specic burden and support
needs, which are oen not adequately addressed by their healthcare pro-
fessionals (HCPs). HCPs oen do not proactively ask for child- and fam-
ily-specic themes due to time pressure and structural barriers as well
as lacking knowledge, condence and competencies. erefore, we devel-
oped and pilot-evaluated a 3-hour training on parenthood and cancer.
e study was conducted as a 3-armed randomized controlled pilot-
trial with three measurement points (baseline, post-training, 3-months
follow-up), comparing face-to-face training (F2F), E-Learning (EL) and
waitlist-control group (CG). Intervention eects were analyzed on HCPs
competency to approach child- and family-related themes, knowledge and
self-ecacy using linear mixed models. Trainings feasibility and accept-
ability were analyzed using descriptive statistics and non-parametric tests.
Study participants (n=152) were mostly female (89%) and psycholo-
gists (38%; physicians 26%; nurses 18%). Main reasons for study partici-
pation were to better address patients needs (90%), to better understand
aected parents and to gain knowledge (55% each). Participants of F2F
and EL were both highly satised with the training. Analyses indicated
positive intervention eects as F2F and EL showed stronger improve-
ments in knowledge and self-ecacy than CG.
Findings demonstrate positive eects of the interdisciplinary train-
ing for both F2F and EL intervention. Since enrollment rates were lower
among physicians and nurses than among psychologists, future imple-
mentation eorts should specically address and encourage those profes-
sions to participate.
Findings show positive intervention eects and indicate training being
an adequate approach to increase HCPs’ knowledge and competencies to
improve their abilities in caring for parents with cancer.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts202
Poster
5
Trauma- and stressor-related disorders among survivors of
hematological malignancies
Peter Esser1; Franziska Springer1; Jochen Ernst1; Katharina Kuba1;
Uwe Platzbecker2; Vladan Vucinic2; Anja Mehnert-Theuerkauf1
1Abteilung für Medizinische Psychologie und Medizinische Soziologie,
Universitätsklinikum Leipzig, Deutschland
2Klinik und Poliklinik für Hämatologie, Zelltherapie und Hämostaseologie,
Universitätsklinikum Leipzig, Leipzig, Deutschland
Background: Trauma- and stressor-related disorders such as posttrau-
matic stress disorder (PTSD) or adjustment disorder (AD) pose a serious
threat for patients with medical conditions. Hematological cancer patients
may face various stressors during their treatment such as stem cell trans-
plantation (SCT) which is associated with multiple distressing events.
Nevertheless, research on the specic types and sources of stressor-related
symptomatology among this patient group is sparse to date.
Methods: Between April 2019 and August 2021, this German cross-sec-
tional study has recruited almost 300 hematological cancer patients,
among which about one half has undergone either autologous or allo-
geneic SCT. Using a structured clinical interview (SCID-5) based on
updated DSM-5 diagnostic criteria, participants are assessed for mental
disorders including PTSD and AD. Descriptive analyses are used to pro-
vide prevalence rates of these disorders and the frequency of disease-re-
lated stressors experienced during treatment.
Result: We will provide results of the rst analyes regarding prevalence
rates of mental disorders including PTSD and AD among both the total
sample and subgroups stratied by treatment (SCT vs. no-SCT) and other
patient characteristics. Analyses will also provide the types and frequency
of disease-related stressors during the disease and treatment trajectory.
Using the updated diagnostic critiera, we will also assess how many and
which type of disease-related stressors reported by the patients meet the
trauma criteria as dened in the DSM-5.
Discussion/Conclusion: Our study will help to inform the health care
system and health care providers about the specic stressor-related bur-
den associated with hematological malignancies and their treatment.
Furthermore, ndings may provide empirical ndings on the question to
which extent the trauma concept may be reasonably applied to this pop-
ulation. ese results will help to establish hypotheses on how treatment
and support programs may be tailored to the specic situation of this
population.
Disclosure Statement: e authors declare no conict of interest.
26
Training needs and barriers of nursing sta in oncology
regarding psycho-oncological screening
Lara Dreismann; Tanja Zimmermann
Medizinische Hochschule Hannover, Klinik für Psychosomatik und
Psychotherapie, Hannover, Deutschland
Background: Psychooncological care can reduce psychological distress
in cancer patients and increase quality of life. Unfortunately, even with
standardized screening tools, early identication of distressed patients
and indication-based treatment are oen missed. One reason may be per-
sonal barriers on the side of the medical team and ambiguities regarding
the screening process. But what are the barriers for nurses in oncology to
perform psychooncological screening? Is there a need for training on the
topic of psychooncological screening?
Methods: N = 15 semi-structured interviews with nursing experts (n =
10 female, 24-62 years) from the oncology departments of the University
Hospitals of Hannover, Leipzig and Dresden were conducted and ana-
lyzed using qualitative content analysis according to Mayring.
Result: Structural barriers like time pressure and missing focus on psy-
chological distress are present. Hurdles on the side of nurses are primar-
ily lack of knowledge and communication uncertainties. e experts
assume a great interest in training. As far as the framework conditions
are concerned, integration into the working hours and the involvement
of the entire nursing team appear to be essential. e content should be
practical, include information on psychological stress, psycho-oncology,
screening process, communication and self-care as well as key phrases for
everyday work and case examples.
Discussion: Despite guidelines, the screening process and information
about psycho-oncological support is not included in the daily nursing ser-
vice catalogue. In addition, patients’ obstacles to referral for psycho-on-
cology should also be considered.
Conclusion: ere is a clear need for training on psycho-oncology,
screening implementation, and communication to overcome knowledge
decites and uncertainties and to establish an interdisciplinary screening
process.
Disclosure Statement: e authors declare no conict of interest.
46
Validation of the psychometric properties of a
“Modied Version of the Hornheider Screening Instrument”
(HSI-MV) using a sample of outpatient and inpatient skin
tumor patients
Britta Buchhold1; Stine Lutze2; Jennis Freyer-Adam1; Michael Jünger2;
Claudia Nordt3; Sebastian Peters3; Stephan Kersting3
1Greifswald, University Medicine , Institute for Medical Psychology, Greifswald,
Deutschland
2Greifswald, University Medicine , Dermatology, Greifswald, Deutschland
3Greifswald, University Medicine, Oncology Center, Greifswald, Deutschland
Purpose: e recognition of psychosocial stress is of great importance
in the treatment of oncological patients. In our Oncology Center, a
tumor-unspecic screening instrument was needed to identify outpa-
tients and inpatients with psychosocial care needs. Among the methods
recommended by the German Working Group for Psychooncology, the
Hornheider Screening Instrument (HSI, questionnaire with 7 items)1
seems to meet our requirements. In clinical practice, the HSI represents
a cost-eective, quickly evaluable, and accepted instrument. e 5th HSI
item, “Is anyone in your family particularly burdened by hospitalization?”
is intended to assess the presence of illness-related family burden. But is
this item equally suitable for outpatients and inpatients? is study inves-
tigated how replacing the original item aects the test performance of this
modied version of the HSI and the assessed family burden.
Methods: 92 outpatients and 98 inpatients with skin tumors assessed their
psychosocial situation using dierent questionnaires.
Results: Compared to the outpatients (9,2%), more than twice as many
inpatients (21,8%) answered “yes” to the item. If the question was replaced
by: “Is anyone in your family particularly burdened by your illness or the
course of your illness?” this setting-related dierence was not evident
(21,6% vs. 25,5%).
Discussion: e “Alternative item” and the “Modied version of the HSI”
(HSI-MV) proved to be superior to the original item and the HSI with
regard to all criteria examined. Psychosocially distressed individuals were
identied with a higher accuracy of hits.
Conclusions: e HSI-MV can be used as a reliable and valid instrument
for the systematic assessment of psychosocial care needs in outpatient and
inpatient settings. Depending on Psychosocial care capacity, a threshold
of ≥5 or ≥4 is appropriate. In addition to screening, support needs should
be inquired about.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 203
Reference:
1 Strittmatter G, Mawick R & Tilkorn M. How to identify patients in need of
psychological intervention. Recent Results Cancer Res. 2002; 160: 353-61.
Disclosure Statement: e authors declare no conict of interest.
156
Dealing with fear of cancer recurrence – evaluation of a
psychooncological group therapy program
Marnie Steinecke; Jana Joachims; Marei Kotzerke; Cathérine Lüke;
Janina Berg; Tanja Zimmermann
Klinik für Psychosomatik und Psychotherapie, Medizinische Hochschule
Hannover, Hannover, Deutschland
Background: Fear of cancer recurrence (FCR) is a common burden for
cancer patients. However, it is oen challenging to nd outpatient psy-
chological support. erefore, for the following study, an outpatient group
adapted from Waadt et al.s manual (2011)1 was developed to focus on spe-
cic needs of oncological patients experiencing FCR.
Methods: e group program consisted of 8 treatment sessions in small-
sized closed groups with 6-8 patients and 2 therapists. e content was
standardized and included behavioral strategies (psychoeducation, cogni-
tive exposure, coping strategies and resources) as well as mindfulness. e
intervention was evaluated by comparing FCR, anxiety and depression
before and aer the group using Wilcoxon-signed-rank-tests.
Result: In total, N = 33 patients with varying oncological diagnoses
participated in the group intervention. Out of these, 26 were female
(76.5%) and 7 were male (20.6%). e mean age was 57.6 years, rang-
ing from 42 to 77 years. A signicant decrease in depression (z=−3.09,
p=.002, n=18), anxiety (z=−3.00, p=.003, n=19) and FCR (z=−2.47,
p = .013, n = 13) was found aer nishing the group intervention.
Moreover, our patients rated the techniques covered in the intervention as
helpful for dealing with FCR and feasible in everyday life.
Discussion: Despite limitations in implementation and recruitment of
patients due to the Corona pandemic, results show positive changes in the
group intervention with respect to FCR, anxiety, and depression.
Conclusion: e results indicate that a structured group therapy program
with a focus on FCR for oncological patients can be an eective and feasi-
ble intervention improving outpatient psychooncological care.
Indication of source:
1 Waadt, S., Duran, G., Berg, P. & Herschbach, P. (2011). Progredienzangst.
Manual zur Behandlung von Zukunsängsten bei chronisch Kranken. Stuttgart:
Schattauer.
Disclosure Statement: e authors declare no conict of interest.
231
Psychological burden after tumor nephrectomy
Marc Heydenreich; Dirk-Henrik Zermann
Vogtland-Klinik Bad Elster, Bad Elster, Deutschland
Background: e diagnosis and therapy of cancer oen results in a psy-
chosocial stress for the aected patient and their families. Holistic reha-
bilitative care includes its evaluation, treatment and psychosocial support.
e aim of the study was to evaluate the psycho-oncological situation of
patients aer nephrectomy.
Methods: 422 patients with an average age of 67.7 years were examined
with the FBK-R23 questionnaire aer nephrectomy at the beginning of a
follow-up rehabilitation.
Result: e data from 422 kidney patients could be evaluated.
Comparison of FBK-values inconspicuous (<34) and noticeable
(>34)– Number of patients who perceived a psychological one-on-one
interview (MW=mean; SD= standard deviation):
FBK<34=14.2 (8.7) (n=367);
FBK>34=48.9 (13.4) (n=55);
psychological one-on-one interview FBK=43.9 (7.6) (n=21)
Comparison of FBK values between men and women:
FBK (men)=15.9 (14.7) (n=250)
FBK (women)=21.0 (16.0) (n=172)
Comparison of the FBK values with regard to the decades of age:
30-49 years: FBK=22.6 (17.7) (n=19)
50-69 years: FBK=19.6 (17.2) (n=221)
70-99 years: FBK=15.4 (12.3) (n=182)
Comparison of FBK values between employees and pensioners:
FBK (employees)=20.4 (16.7) (n=209)
FBK (pensioners)=15.5 (13.6) (n=213)
Discussion: 13% of the examined patients had abnormal FBK-23 ques-
tionnaire values and thus a signicant need for psycho-oncological treat-
ment. Women and younger / working patients are more oen aected.
Conclusion: Psychosocial treatment oers for patients aer nephrectomy
must be further developed and adapted. In the aercare the physician has
a clear responsibility for the psychosocial care of the patient.
Disclosure Statement: e authors declare no conict of interest.
297
The impact of the COVID-19 pandemic on outpatient cancer
patients
Tamara Frank1,2; Theresia Pichler1; Sabrina Maier1; Ineke Batenhorst1;
Tanja Daltrozzo2; Nadia Harbeck1,3; Hana Algül1; Volker Heinemann1,4;
Kerstin Hermelink5; Andreas Dinkel2; Friederike Mumm1,4
1Comprehensive Cancer Center München, München, Deutschland
2Klinik und Poliklinik für Psychosomatische Medizin und Psychotherapie,
Klinikum rechts der Isar, Fakultät für Medizin, Technische Universität München,
München, Deutschland
3Brustzentrum, Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe,
Klinikum der Universität München, LMU München, München, Deutschland
4Medizinische Klinik und Poliklinik III, Klinikum der Universität München, LMU
München, München, Deutschland
5Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Klinikum der
Universität München, LMU München, München, Deutschland
Background: e COVID-19 pandemic has led to higher levels of stress,
anxiety and depression in the population. Oncological patients might be
particularly vulnerable, since structural changes and limited resources
within medical care might aect treatment. Besides, due to their under-
lying condition, most are at-risk patients. e aim of this study was to
identify the specic stressors and current needs of cancer patients.
Methods: Between 11/2020 and 02/2021 122 outpatient cancer patients of
the Comprehensive Cancer Center Munich participated in the study aer
giving informed consent. Based on a standardized, semi-structured inter-
view, participants were asked about their knowledge and concerns about
COVID-19, risk perception, condence in the national health system
and readiness to get vaccinated against COVID-19. Psychosocial distress,
symptoms of anxiety and depression, somatic symptoms and self-ecacy
were collected via standardized questionnaires. Additionally, socio-demo-
graphic and medical data were collected.
Result: More than a third of the patients (34.2%, n = 41) require addi-
tional information about the eects of the coronavirus on their cancer
and/or treatment. Patients most oen mentioned unanswered questions
regarding the impact of a COVID-19- infection on cancer, followed by
vaccination and treatment. About 17% had faced changes concerning
their current or planned treatment. 34.7% (n=42) of the patients were
signicantly distressed (mean distress score: 3.7; scale: 0-10). A possi-
ble overload of the health care system was the most commonly reported,
COVID-related fear (77.9%).
Discussion: Findings suggest that oncologists should educate and support
patients by exploring and responding to their diverse questions regarding
the eect of COVID-19 on their disease and treatment.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts204
Conclusion: Providing emotional support and oering reliable sources of
information can help cancer patients navigate through uncertainties and
reduce anxiety.
Presented at: IPOS 2021, DKPM 2021, DGHO 2021, PSO 2021
Disclosure Statement: e authors declare no conict of interest.
313
Do cancer patients benet from talking to cancer survivors?
Lessons learned from the German integrated, cross-sectoral
psycho-oncology programme (isPO)
Vera Schiewer1; Anne Klein1; Hildegard Labouvie1; Hedy Kerek-Bodden2;
Michael Kusch1
1Klinik I für Innere Medzin, Universitätsklinikum Köln, Klinische
Psychoonkologie/ Versorgungsforschung, Köln, Deutschland
2Haus der Krebs-Selbsthilfe - Bundesverband e.V., Bonn, Deutschland
Background: e project isPO, integrated cross-sectoral psycho-on-
cology, funded by the innovation fund at the G-BA, is investigating the
quality of the stepped-care-programme isPO. As part of the programme,
long-term cancer survivors (isPO-Oncoguides) inform cancer patients
undergoing active treatment about psychosocial aspects of cancer in a
timely and personal manner. e quality and helpfulness of these patient
information conversations has not been investigated so far.
Methods: Long-term cancer survivors were qualied and certied as
so-called isPO-Oncoguides (OG) by the German Cancer Self-Help
Association. To assess the quality and helpfulness of the personal conver-
sation of the patient and the OG, evaluation sheets are used. e sheets
are completed by the OG immediately aer the conversation and by the
patient within 1 to 3 months. e evaluation sheet consists of two ques-
tions on the quality of the conversation: a) the appropriateness of the
timing of the contact, b) the degree of condence conveyed and two ques-
tions on the helpfulness of the conversation: a) helpfulness for orientation
regarding cancer and b) perceived support in coping with cancer.
Result: So far 340 OGs and 220 patients completed the evaluation sheet.
Preliminary analyses show that 92% of the patients and 70% of the OG
answered at least one of the four questions. e assessment of the personal
contact and conversation is predominantly rated as positive by both the
patients and the OGs. Analyses of the concordance of OG and patient
assessment reveal discrepancies, especially when patients rate the quality
and helpfulness of the conversation with OG’s negatively.
Discussion: e presentation will discuss the ndings of the benets of
conversations between patients with cancer and long-term cancer survi-
vors in the early stages of cancer therapy.
Conclusion: Cancer patients in active treatment benet from the personal
contact and conversation with long-term cancer survivors.
Disclosure Statement: e authors declare no conict of interest.
324
The eect of eHealth interventions on psychosocial distress,
coping strategies, quality of life and unmet supportive care
needs among cancer patients during acute treatment stage.
A rapid review
Miriam Grapp1; Senta Kiermeier1; Karin Jordan2;
Hans-Christoph Friederich3; Imad Maatouk1
1Universitätsklinik Heidelberg, Klinik für Allgemeine Innere Medizin und
Psychosomatik, Psychoonkologische Ambulanz am NCT, Heidelberg,
Deutschland
2Universitätsklinik Heidelberg, Abteilung Innere Medizin V, Hämatologie,
Onkologie und Rheumatologie, Heidelberg, Deutschland
3Universitätsklinik Heidelberg, Klinik für Allgemeine Innere Medizin und
Psychosomatik, Heidelberg, Deutschland
Background: In recent years, an increasing number of eHealth interven-
tions have been developed for cancer patients under anticancer treat-
ment. Few reviews already exist in this eld, focusing mainly on symptom
tracking and symptom management. erefore, we conducted a rapid
review of the impact of eHealth interventions on psychological distress
(general distress, depression, anxiety), coping strategies, quality of life
(QoL) and unmet psychosocial care needs among cancer patients during
treatment.
Methods: e review followed the reporting guidelines outlined in the
PRISMA statement and was registered at the International Prospective
Register of Systematic Reviews (PROSPERO). Cochrane Library,
MEDLINE, PsycINFO and PSYNDEX were systematically searched.
Included were randomized controlled trials (RCTs), reviews and
meta-analyses.
Result: A total of 28 studies which met the eligibility criteria – 10 system-
atic reviews and 18 randomized clinical trials – were considered for this
rapid review. e included studies were published from 2011-2020, with
21 of 28 studies being from 2018 or later. Both reviews and RCTs showed
a high degree of heterogeneity regarding type of intervention, character-
istics of the target population (tumor entity, time since diagnosis, type of
treatment), and outcomes used.
Discussion: Overall, the evidence is encouraging, but limited. ere are
partial positive eects, especially for quality of life, depression and anxiety.
However, due to the observed heterogeneity and methodological prob-
lems of the individual studies, no clear evidence can be derived.
Conclusion: eHealth interventions seem to have great potential to
improve psychological distress, especially in patients that are otherwise
underserved. In order to improve the quality and strength of current
research guidelines/recommendations are urgently needed for both the
development of eHealth interventions and their evaluation.
Disclosure Statement: e authors declare no conict of interest.
360
Screening and psycho-oncological support in patients with
head and neck cancer and brain malignancies before radiation
with mask xation: a feasibility study of a multidisciplinary
care program
Sebastian Adeberg1; Christina Sauer2; Sebastian Regnery1; Paul Windisch1;
Christoph Nikendei2; Johannes Ehrenthal2; Rami El Shae1,3;
Juliane Hörner-Rieber1; Laila König1; Sati Akbaba4; Kristin Lang1;
Thomas Held1; Karim Zaoui5; Julius Moratin6; Christian Freudlsperger6;
Stefan Rieken1,3; Jürgen Peter Debus1; Hans-Christoph Friederich2;
Imad Maatouk2
1Heidelberg, University Hospital Heidelberg , Department of Radiation
Oncology, Heidelberg, Deutschland
2Heidelberg, University Hospital Heidelberg , Department of General Internal
Medicine and Psychosomatics, Heidelberg, Deutschland
3University Hospital Göttingen, Department of Radiation Oncology, Göttingen,
Deutschland
4Mainz, University Hospital Mainz, Department of Radiation Oncology, Mainz,
Deutschland
5Heidelberg, University Hospital Heidelberg, Department of
Otorhinolaryngology, Head and Neck Surgery, Heidelberg, Deutschland
6Heidelberg, University Hospital Heidelberg, Department of Oral and
Maxillofacial Surgery, Heidelberg, Deutschland
e present single-center, single-arm trial investigates the feasibility of a
multidisciplinary care program, which aims to reduce psychological dis-
tress and to improve compliance in patients with head and neck cancer
or brain malignancies undergoing radiotherapy with mask-xation. Our
care program comprised (1) a screening and (2) the provision of a psy-
cho-oncological intervention using imaginative stabilization techniques
for distressed patients and/or in case of subjective needs. Physicians could
also directly assign patients to the intervention. Of the n = 1020 screened
patients, n = 257 patients indicated a distress ≥ 5, and n = 141 patients
reported panic attacks. 25% of asked patients reported a subjective inter-
est in psycho-oncological support. In sum, 35 patients received the psy-
cho-oncological intervention, whereof 74% were assigned by radiation
oncologists. In this small patient cohort no signicant pre-post eects of
the intervention could be detected. Our results indicate good feasibility
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 205
of a multidisciplinary care program for patients before radiotherapy with
mask-xations. e screening results underline the high psychological
distress and demand of psycho-oncological support. However, as the
utilization of our intervention was low, future studies should investigate
barriers and improve compliance for psycho-oncological services in these
patients.
Disclosure Statement: e authors declare no conict of interest.
386
Eectiveness of a Video Sequence based Intervention on
Anxiety, Fatigue and Depression in Cancer Patients
Elisabeth Jentschke; Sven Neubert; Sina Schlecht; Antonia Rabe
Universitätsklinikum Würzburg, Comprehensive Cancer Center Mainfranken,
Psychoonkologie , Würzburg, Deutschland
Background: Many cancer patients suer from psychological problems,
most notably anxiety and depression1 as well as cancer-related fatigue2.
e COVID-19 pandemic may further worsen mental health3 and com-
plicate psycho-oncological care. is study examines the short- and
long-term eects of a video intervention, including psychoeducation and
practical exercises on anxiety, depression and fatigue.
Methods: Participants will be randomly assigned to an intervention
group, receiving the video intervention rst or a control group, receiv-
ing it subsequently. e intervention lasts four weeks and is structured in
eight video sequences. Anxiety, depression, and fatigue are measured by
validated questionnaires at three measurement points (before and aer
the intervention, 3 months aer the end of the intervention).e control
group receives an additional questionnaire at the beginning of the waiting
period.
Result: 172 patients (86 per group) with mixed cancer diagnoses were
included in the study. e study is recently conducted. It is expected that
cancer patients who participate in the video intervention will experience a
decrease in symptoms or at least no worsening.
Discussion: Oering and evaluating the eects of digital interventions
seems all the more relevant during the COVID-19 pandemic. With the
pandemic inuencing mental health issues, the validity of the outcomes
may be limited.
Conclusion: If the video sequence based intervention could reduce anxi-
ety, depression and fatigue, this type of therapy could expand psycho-on-
cological care.
References:
1 Kuhnt S et al.Twelve-Month and Lifetime Prevalence ofMental Disorders
in Cancer Patients. Psychother Psychosom.2016;85(5):289-96.
2 Mehnert A et al. One in two cancer patients is signicantly dis-
tressed: Prevalence and indicators of distress. Psychooncology. 2018
Jan;27(1):75-82.
3 Torales J, O’Higgins M, Castaldelli-Maia JM, Ventriglio A. e out-
break of COVID-19 coronavirus and its impact on global mental
health. Int J Soc Psychiatry. 2020;66(4):317-320.
Disclosure Statement: e authors declare no conict of interest.
485
The Yinota-trial: Ecacy of Yoga-intervention in high grade
glioma patients and their caregivers – patient-reported
outcomes and serum stress parameters
Elisabeth Jentschke1; Antonia Rabe1; Carsten Hagemann2; Jörg Schubert3;
Celine Dudas4; Johanna Weth1; Almuth F. Keßler5
1Universitätsklinikum Würzburg, Comprehensive Cancer Center Mainfranken,
Psychoonkologie, Würzburg, Deutschland
2Universitätsklinikum Würzburg, Neurochirurgische Klinik und Poliklinik des
Universitätsklinikums, Funktionbereich Tumorlabor, Würzburg, Deutschland
3Universitätsklinikum Würzburg, Zentrum Innere Medizin, Zentrallabor -
Gerinnungsambulanz, Würzburg, Deutschland
4Universitätsklinikum Würzburg, Neurochirurgische Klinik und Poliklinik des
Universitätsklinikums , Tumorbiologisches Labor , Würzburg, Deutschland
5Universitätsklinikum Würzburg, Neurochirurgische Klinik und Poliklinik des
Universitätsklinikums, Neurochirurgie, Würzburg, Deutschland
Background: High-grade glioma patients and their caregivers oen suer
from psychological distress.1 Nevertheless, supportive services are lacking.
is study investigates whether a mindfulness-based yoga intervention is
feasible and aects anxiety, depression, quality of life, and stress-associ-
ated physiological parameters.
Methods: A monocentric on-site pilot study to test feasibility was started
in 2020 and then adapted to an online format due to the COVID-19 pan-
demic. Participants were randomly assigned to immediate intervention
and 8-weeks wait-list control groups. At randomization, immediately
before and aer the end of the 8-week intervention (1 h/week), which
was performed by trained yoga teachers in a synchronous format, as well
as another 3 months later, validated questionnaires were lled by partic-
ipants and serum plus saliva samples were taken. In addition, participants
were asked to rate their satisfaction with various course features.
Results: A total of 43 participants with 27 donating biological samples
and a drop-out of 14 were included. No signicant changes in subjective
criteria and physiological stress parameters were detected. Known disad-
vantages of online interventions were reported, e.g. technical diculties.
Overall course-satisfaction, with teachers guidance most positively rated,
was reported.
Discussion: High-grade glioma patients are very vulnerable due to their
rapidly changing health status. Caregivers oen have very limited time
due to the care they provide. erefore, recruitment is dicult and leads
to dropouts. Validity of the results may be limited due to the small sample
size and comparability of stress parameters due to circadian uctuations
in salivary cortisol.
Conclusion: e online yoga course is feasible. Despite of lacking per-
sonal contact, supervision of participants is possible and satisfactory. To
measure cortisol, more reliable hair samples will be taken in the upcoming
multicenter study, starting in fall 2021.
Indication of source: 1 Renovanz M et al. Front Neurol 2018
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts206
569
Qualitative interview study to assess care needs among
aected with Li-Fraumeni syndrome in Germany
Sarah Schott1; Juliane Nees1; Senta Kiermeier2; Imad Maatouk2
1Heidelberg, Universitätsfrauenklinik, Heidelberg, Deutschland
2Heidelberg, Klinik für Allgemeine Innere Medizin und Psychosomatik,
Heidelberg, Deutschland
Purpose: Li-Fraumeni syndrome (LFS) is a rare cancer predisposition
syndrome with a lifetime risk of up to 100% suering at least one malig-
nancy from birth onwards. Aected people claim distress and insucient
surveillance structures. Yet, little is known about LFS specic needs within
Germany.
Methods: A qualitative study was conducted to assess the needs of the
target group in order to develop an online intervention to support this
underserved group. Adults with a (likely) pathogenic TP53 variant could
participate with written consent. A study-specic semi-structured inter-
view guide was developed based on clinical experience and literature.
e guideline examined experiences and attitudes towards surveillance,
psychosocial stress and care, media, health system, participatory deci-
sion-making and issues regarding social environment (family; partner/
friends; career).
All interviews were conducted by one psychologist. Interviews were
transcribed verbatim. Qualitative content analysis of the transcribed
interviews was performed based on the principles of inductive and deduc-
tive category development.
Results: Between March - October 2020, 20 interviewees (f: 17; m: 3) aged
25 -67 (median 36) were enrolled. Most participants had suered cancer
themselves (85%) and had either children with childhood cancer (15%) or
parents and/or siblings with a diagnosis of LFS (68%).
irteen categories, summarized in four overarching topics were iden-
tied: e.g. fear of progression and distress, care supply, communication,
LFS in everyday life.
Discussion: People with LFS have overlapping issues in everyday life, pri-
vately and socially dealing and coping with their diagnosis. Comprehensive
care needs can be derived from the results, which are to be addressed in a
further step within the framework of an online intervention.
Conclusion: Specic communicative strategies and interdisciplinary sup-
ply structures are need in order to reduce the burden of LFS.
Funding: Federal Ministry of Education and Research ADDRESS Project
Grant Number: 01GM1909D
Disclosure Statement: e authors declare no conict of interest.
610
Web-based cognitive behavioral therapy for cancer-related
fatigue among survivors of Hodgkin lymphoma – a feasibility
study
Peter Esser1; Horst Müller2; Peter Borchmann2; Stefanie Kreissl2;
Uwe Platzbecker3; Vladan Vucinic3; Hans Knoop4;
Anja Mehnert-Theuerkauf1
1Abteilung für Medizinische Psychologie und Medizinische Soziologie,
Universitätsklinikum Leipzig, Leipzig, Deutschland
2Deutsche Hodgkin Studiengruppe, Klinik I für Innere Medizin,
Universitätsklinikum Köln, Köln, Deutschland
3Klinik und Poliklinik für Hämatologie, Zelltherapie und Hämostaseologie,
Universitätsklinikum Leipzig, Leipzig, Deutschland
4Abteilung für Medizinische Psychologie, Universitätsklinikum Amsterdam,
Amsterdam, Niederlande
Background: Hodgkin lymphoma is the most frequent malignancy in
young adults. Even though many patients can be cured, cancer-related
fatigue (CRF) is a frequent cause for long-term morbidity. We investi-
gated the feasibility of a web-based cognitive-behavioral therapy (CBT) to
reduce severe CRF among HL survivors.
Methods: We conducted a bi-centric before-and-aer study to adapt and
preliminary test the CBT among severely fatigued HL survivors. Patients
were primarily recruited via the German Hodgkin Study Group (GHSG)
and assessed at baseline (t0), post-treatment (t1) and 3-months follow-up
(t2). We primarily analysed feasibility including response and drop-out
rate. Secondary outcomes assessed preliminary ecacy including CRF
(CIS-Fat and EORTC-QLQ FA-12), quality of life (QoL; EORTC-QLQ
C30) and depressive symptomatology (PHQ-9). T-tests were used to com-
pare baseline with t1 and t2, respectively.
Results: Among 79 eligible patients contacted via the GHSG, 33 provided
initial interest (response rate: 42 %). Of the 17 participants, four patients
were treated face-to-face as pilot patients, 13 patients underwent the web-
based version. Ten patients completed the treatment (drop-out rate: 41
%). Intent-to-treat analyses revealed signicant improvements in both
CRF scores, depressive symptomatology and QoL (p ≤ .03). e eects in
CIS-Fat remained signicant at t2 (p = .03). Except for QoL, eects at t1
were replicated among the eight completers of the online version (p ≤ .04).
Discussion/conclusion: We found preliminary ecacy of the program
which warrants further research. Results on feasibility will help to design
a future RCT.
Disclosure Statement: e authors declare no conict of interest.
616
Depression; anxiety and distress screeners on the need and
utilization of psychosocial services among cancer survivors
Franziska Springer1; Leon Sautier2; Georgia Schilling3; Uwe Koch-Gromus2;
Carsten Bokemeyer3; Michael Friedrich1; Anja Mehnert-Theuerkauf1;
Peter Esser1
1University Medical Center Leipzig, Department of Medical Psychology and
Medical Sociology, Leipzig, Deutschland
2University Medical Center Hamburg-Eppendorf, Department of Medical
Psychology, Hamburg, Deutschland
3Department of Oncology, Hematology, and Bone Marrow Transplantation
with Section of Pneumology, University Medical Center Hamburg‐Eppendorf,
Hamburg, Deutschland
Background: Distress screening is recommended within routine clini-
cal cancer care to identify patients in need for psychosocial support. It is
however not clear whether distress screeners can be used for appropriate
psychosocial care planning and thus whether they can predict dierent
levels of readiness to use psychosocial support.
Methods: In a secondary analysis of a cluster intervention study, adult
cancer patients were assessed with three established distress screeners (DT,
PHQ-9, GAD-7) at baseline. e levels of readiness to use psychosocial
support, that is, need, intention and utilization, were binary assessed for
dierent psychosocial services aer 3 and 6 months. Logistic regression
models were applied to investigate the predictive eect of the screeners
on the levels of readiness. All models were corrected for multiple testing.
Result: 660 patients were included in the study, 46% were female and the
average age was 60 years. At the 3-month and 6-month follow-up, 353 and
259 patients participated, respectively. e PHQ-9 and GAD-7 predicted
the levels of readiness more oen than the DT did. Generally, the screen-
ers were best in predicting the need of the services, while the actual uti-
lization of the services was not predicted by any of the distress screeners.
Discussion and Conclusion: e three distress screeners might be useful
in psychosocial care planning, as they are all able to predict the need for
psychosocial support, and the PHQ-9 and GAD-7 further predict to some
degree the intention to use psychosocial support. Future research needs
to examine potential barriers and supporting factors that may explain the
utilization of psychosocial services.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 207
699
Psychosocial aftercare of adolescent and young adult cancer
survivors in Germany: Awareness, utilisation, satisfaction and
associated factors
Annekathrin Sender1; Michael Friedrich1; Katja Leuteritz1; Diana Richter1;
Florian Lordick2; Kristina Geue1
1University of Leipzig, Department of Mental Health, Medical Psychology and
Medical Sociology, Leipzig, Deutschland
2University of Leipzig, Medical Center, University Cancer Center, Leipzig,
Deutschland
Background: Young adult cancer patients have come into scientic focus
in recent years due to their high survival rate, among other things, but
also due to an increased psychological burden. Research ndings indicate
a lack of adequate care, and to date oer little insight into the current psy-
chosocial care situation. is study systematically assesses the awareness
of, utilisation of and satisfaction with psychosocial care for young adult
cancer survivors.
Methods: Survivors between 18 and 39 years were surveyed in aercare.
Awareness of, utilisation of and satisfaction with psychological coun-
selling (PC), social-legal counselling (SLC) and other psychosocial care
(OPC) were measured using self‐developed questionnaires. Multivariate
analyses were conducted to determine factors correlated with awareness
and use of psychosocial care.
Result: 514 survivors participated; the mean age at diagnosis was 29.6
years (SD=6.14). 54% of cancer survivors were aware of PC, 45% of SLC
and 24% of OPC. ose who possessed knowledge about these services
used it to a considerable extent (63%–74%), and the majority (66%–75%)
was highly satised. No common factors could be found that increase
the likelihood of being aware of these three services (R2 = 0.028–0.138).
Female gender (OR=2.08–2.18) and high anxiety (OR=1.19–1.38) were
identied as common factors that increase the likelihood of utilising psy-
chosocial services (R2 = 0.160–0.395).
Discussion: Survivors who are aware of psychosocial services in aercare
are motivated to use them and express high satisfaction with use. For the
utilisation of psychosocial services, anxiety and female gender can be
identied as common factors.
Conclusion: e visibility of psychosocial services for aercare should be
increased given the high number of unaware young adult survivors. e
active and repeated addressing of psychosocial issues and regular provi-
sion of information (e.g., written guides on survivorship) by caregivers
should be made a standard of care for this group.
Disclosure Statement: e authors declare the following: Förderung durch die
Deutsche Krebshilfe (Grant No.: 110948).
705
The components of the new form of care isPO: Result of the
innovation fund project on integrated, cross-sectoral
psycho-oncology
Hildegard Labouvie1; Vera Schiewer1; Natalie Talalaev1; Anne Klein1;
Peter Haas2; Michael Kusch1
1Klinik I für Innere Medizin, Universitätsklinik Köln, Klinische Psychoonkologie/
Versorgungsforschung, Köln, Deutschland
2Medizinische Informatik, Fachhochschule Dortmund, Dortmund, Deutschland
Background: e Innovation Fund at the G-BA funded the project
isPO/’’Integrated, cross-sectoral psychooncology’’ for 54 months between
2017 and 2022 with approx. 9 million EURO. e result of the project is
the „new form of care isPO“ (nFC-isPO). According to the Innovation
Fund, the nFC-isPO can be oered nationwide if successful.
Methods: e nFC-isPO, which consists of a total of 6 components, was
developed on the basis of the evaluation model according to Issel [1] and
implemented at four locations in NRW. In order to demonstrate whether
the form of care meets the requirements for transfer into the German
health care system, the components were designed in relation to the
Framework for planning and delivery of psychosocial oncology services of
the “American Psychosocial Oncology Society task force” [2].
Result: e nFC-isPO consists of six components (C1-C6) that are avail-
able in care telematic form in order to be implemented in the standard care
of the German health care system. e components (C) include C1) health
care concept, C2) health care pathways, C3) health care network con-
cept, C4) health care management, C5) the „Computer-based Assistance
System: Psycho-Oncology“ and C6) IT-supported quality management.
Discussion: e six components of the nFC-isPO and their relation to the
framework of the APOS task force are presented.
Conclusion: e innovative nFC-isPO is designed according to interna-
tional standards of the APOS task force.
References:
1 Issel, LM (2014). Health program planning and evaluation: A practi-
cal, systematic approach for community health. Burlington, MA: Jones
& Bartlett Learning
2 Pirl WF, Greer JA, Gregorio SW-D et al. (2020). Framework for plan-
ning the delivery of psychosocial oncology services: An American
psychosocial oncology society task force report. Psycho-Oncology.
2020;29:1982-1987
Disclosure Statement: e authors declare no conict of interest.
717
Evaluation of the new form of care isPO using the framework
for planning the delivery of psychosocial oncology services
of the American Psychosocial Oncology Society (APOS) task
force
Michael Kusch1; Hildegard Labouvie1; Vera Schiewer1; Clarissa Lemmen2;
Peter Haas3
1Klinik I für Innere Medizin, Universitätsklinikum Köln, Klinische
Psychoonkologie/Versorgungsforschung, Köln, Deutschland
2Institut für Gesundheitsökonomie u. Klinische Epidemiologie der Universität zu
Köln, Universitätsklinikum Köln, Köln, Deutschland
3Medizinische Informatik, Fachhochschule Dortmund, Dortmund, Deutschland
Background: In 2020, the American Psychosocial Oncology Society
(APOS [1]) task force formulated the framework for planning the delivery
of psychosocial oncology services that could aid in planning services and
justifying requests for resources. e project isPO/integrated, cross-sec-
toral psycho-oncology, funded by the Innovation Fund of the G-BA,
aimed to develop a new form of care (nFC-isPO) that has the prospect
of being oered nationwide. e quality features of the nFC-isPO were
evaluated by an independent institute in 2018-21. e presentation will
answer the question of whether the quality features of the nFC-isPO also
meet the requirements of the APOS task force.
Methods: e nFC-isPO was developed according to Issel’s evaluation
theory [2] and implemented at four sites in NRW within a contract for
„special care“ according to § 140a SGB V. Quarterly quality circles (QC)
and quality workshops (QW) for quality improvement were conducted.
e quality improvement process of the nVF-isPO took place within the
framework of PDC/SA (plan, do check/study act) cycles and evaluation
reports by an independent evaluation institute.
Results: In a period of 27 months, 11 site-intern QC’s and 11 cross-site
QW’s were carried out, which were followed by a total of 18 PDC/SA
cycles for continuous quality improvement. e independent evaluation
institute submitted one prospective, two formative and one summative
report on the quality of care of the nVF-isPO. All results have to be evalu-
ated against the framework of the APOS task force.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts208
Discussion: In the presentation, the conformity of the nFC-isPO with the
APOS criteria will be presented and critically evaluated.
Conclusions: e quality of care of nFC-isPO meets the criteria of the
APOS task force.
References:
1 Pirl WF et al. (2020). Framework for planning the delivery of psycho-
social oncology services: An American psychosocial oncology society
task force report. Psycho-Oncology. 2020;29:1982-1987.
2 Issel, LM (2014). Health program planning and evaluation: A practi-
cal, systematic approach for community health. Burlington: Jones &
Bartlett Learning.
Disclosure Statement: e authors declare no conict of interest.
722
Causal attributions, controllability and changes in health
behavior among women carrying a BRCA1/2-mutation
Katharina Klein1; Dorothee Speiser2; Hannah Brand1; Friederike Kendel1
1Charité – Universitätsmedizin Berlin, Institute of Gender in Medicine, Berlin,
Deutschland
2Charité – Universitätsmedizin Berlin, Department of Gynecology with Breast
Cancer, Berlin, Deutschland
Background: Health behavior is becoming increasingly important for
women carrying a BRCA1/2-mutation regarding the ability to inuence a
disease. Furthermore, it is necessary to clarify whether women are aware
of the causes of cancer, as their assumptions do not always align with the
medical evidence. e aim of the study was to investigate which causal
attributions BRCA1/2-mutation carriers make and if they assume that
they can inuence the development of (renewed) cancer through preven-
tion measures and their health behavior. Additionally, it should be inves-
tigated whether BRCA1/2-mutation carriers have changed their health
behavior.
Methods: As part of a cross-sectional questionnaire study, women carry-
ing a BRCA1/2-mutation (N=100) were asked about causal attributions,
controllability and changes in health behavior. In the statistical analysis,
descriptive statistical methods, t- and chi-square tests as well as correla-
tion analyzes were applied and calculated.
Result: In addition to heredity (97.0%), the women also named stress
(82.0%), health behavior (82.0%), environmental factors (80.0%) and
personality (62.0%) as causes for cancer. Most of the study participants
believed that they could inuence their own disease risk to a large extent.
With regards to individual health behaviors, the women ate healthier
(p<.001), were more physically active (p=.004) and tried to keep their
stress level low (p=.003). Causal attribution and controllability were asso-
ciated with changes in health behavior.
Discussion: e results demonstrate the importance of incorporating
behavior information into health care as well as specically asking women
what they perceive to be the causes of cancer.
Conclusion: e study underlines the importance of subjective param-
eters for the adaptation to a life with a BRCA1/2-mutation and shows
a great need for research in this regard, e.g. with regard to digital sup-
port oers in care from a medical, psychological and also health science
perspective.
Disclosure Statement: e authors declare that they have no conict of interest.
731
A comparative analysis of the long-term eects of cancer
therapy on survivors enrolled in the University Cancer Center
Hamburg (UCCH) Clinical Survivorship Registry: a cohort
study
Carrie-Ann Minto1; Barbara Koch1; Ann-Kathrin Ozga2;
Antonia Beitzen-Heineke1; Sarah Dwinger3; Marianne Sinn1;
Carsten Bokemeyer1; Alexander Stein1; Julia Mann1; Jannike Salchow1
1Universitätsklinikum Hamburg Eppendorf, II. Medizinischen Klinik und
Poliklinik (Onkologie, Hämatologie, Knochenmarktransplantation mit Abteilung
für Pneumologie), Hamburg, Deutschland
2Universitätsklinikum Hamburg Eppendorf, Zentrum für Experimentelle
Medizin, Institut für Medizinische Biometrie und Epidemiologie, Hamburg,
Deutschland
3Universitätsklinikum Hamburg Eppendorf, Zentrum für Psychosoziale Medizin,
Institut und Poliklinik für Medizinische Psychologie, Hamburg, Deutschland
Background: As cancer rates increase and mortality decreases, the num-
ber of survivors will rise. Cancer therapy causes lasting side-eects that
impact well-being. is study aims to report prevalences of distress,
depression, anxiety, fatigue and level of unmet needs; and assess the inu-
ence of age, sex, primary diagnosis, treatment modality (TM) and time
since diagnosis (TSD).
Methods: Subjects were recruited from the UCCH survivorship program
and at rst appointment completed 5 questionnaires (DT, SCNS-SF34,
PHQ-9, GAD-7 & FACIT-F). Demographics and prevalences were
reported for the group and selected cohorts (age: 18-39, 40-64, 65+; sex;
primary diagnosis: lymphoma, leukemia, gastrointestinal, gynecological,
sarcoma, other; TM: multimodal, local, systemic; TSD: 0-2, 3-5, 6-10, 10+
years). Multivariable linear/logistic regression and pairwise comparison
were run on cohorts to assess the odds of reporting clinically relevant out-
come levels.
Results: From Jan. 2015 to Mar. 2020 449 survivors were screened - 435
included. Overall, 57.2% reported clinically relevant distress levels. For
depression: mild (30.1%), moderate (15.4%), moderately-severe (5.3%)
and severe (1.8%) symptoms were reported. 78% reported the likely pres-
ence of an anxiety disorder. 29.2% reported clinically signicant fatigue.
Mean summated Likert scores ±SD for unmet needs: psychological
19.97±10.497, health systems & information 23.62±13.939, physical &
daily living 9.19±4.607, patient care & support 8.30±4.592 and sexuality
5.01±3.062. e impact analysis indicated that age and primary diagnosis
had the greatest inuence, followed by sex, TSD and TM.
Discussion: In most outcomes over half of respondents reported clini-
cally relevant levels, showing how strongly the long-term eects of ther-
apy aect survivors. Whilst the impact analysis provides key insights into
what did, and perhaps more interestingly, did not strongly inuence the
outcomes.
Conclusions: Based on the ndings, future research could seek to better
understand the inuence of age, sex, diagnosis, TM and TSD.
Disclosure Statement: e authors declare no conict of interest.
743
Transferabillity of the new form of care isPO into the German
health care system
Michael Kusch; Vera Schiewer; Hildegard Labouvie
Klinik I für Innere Medizin, Universitätsklinikum Köln, Klinische
Psychoonkologie/Versorgungsforschung, Köln, Deutschland
Background: e Innovation Fund (IF) has funded the project isPO/
integrated, cross-sectoral psycho-oncology. e project was intended to
implement the goal of the National Cancer Plan to further develop „onco-
logical care structures and quality assurance. In the isPO project, a new
form of care (nFC-isPO) was developed and implemented. According to
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 209
the IF, the nFC-isPO project could be oered nationwide if successful. e
structure and process quality of the nFC-isPO was evaluated by an inde-
pendent Institute of Medical Sociology, Health Services Research, and
Rehabilitation Science (IMVR) in the period 2018-2021. In addition, the
management of the isPO consortium has checked whether the nFC-isPO
meets the requirements of the American Psychosocial Oncology Society
(APOS) task force for high quality psychosocial oncology services [1].
Methods: During the one-year development phase of isPO (2018), the
IMVR used methods of prospective evaluation to test the implementabil-
ity of the nFC-isPO. In the two-year implementation phase (2019-2020),
nFC-isPO was provided under selective contract conditions (§ 140a SGB
V). e IMVR used formative evaluation methods to examine the condi-
tions under which nVF-isPO could be transferred to standard care. e
APOS task force requirements for high quality psychosocial oncology ser-
vices were reviewed taking into account the ndings from the evaluation
of the nFC-isPO.
Results: e nal summative evaluation report of the IMVR will be
completed in April 2022. Even though the report is not yet available, it is
already possible to demonstrate the transferability of the nFC-isPO into
the German health care system.
Discussion: e transferability of the nFC-isPO to selective-con-
tract-based care in the German health system will be presented.
Conclusions: e nFC-isPO can serve as a model for the transfer of psy-
cho-oncology into the German health care system.
Reference:
1 Pirl WF et al. (2020). Framework for planning the delivery of psycho-
social oncology services: An American psychosocial oncology society
task force report. Psycho-Oncology,29:1982-1987.
Disclosure Statement: e authors declare no conict of interest.
762
Evaluation of the access process to psycho-oncology
care:results from the German integrated, cross-sectoral
psycho-oncology programme (isPO)
Anne Klein; Vera Schiewer; Hildegard Labouvie; Michael Kusch
Klinik I für Innere Medizin, Universitätsklinik Köln, Klinische Psychoonkologie/
Versorgungsforschung, Köln, Deutschland
Background: e Innovation Fund at the G-BA funds the project isPO
(integrated, cross-sectoral psycho-oncology). e project is intended to
implement the demand of the Federal Government’s National Cancer
Plan to further develop “oncological care structures and quality assur-
ance” [1]. Although many cancer patients experience high levels of emo-
tional distress, only a small proportion make use of psycho-oncological
care (POC). One reason is that the process of referral to POC has not been
uniformly structured in oncology centers so far. Within the framework of
the isPO program, care pathways for the access process (AP) have been
formulated to ensure the accessibility and timeliness of POC according to
the quality indicators of the ÄZQ [2].
Methods: To ensure a timely access to POC, referral bills have been devel-
oped. Using the referral bills, the attending physician informs a patient
about POC, records the patients subjective need to participate and initi-
ates POC. Specic dates in the AP such as admission date, date of med-
ical information, referral and patient enrolment were documented. e
quality criteria accessibility and timeliness and program adherence were
investigated using a mixed methods design.
Result: Preliminary results show that 2.257 patients were assigned to
the nfc-isPO within 12 months. e rates of accessibility vary per clinic
between 0% and 31,4%. of the initial access process showed an average
process duration of 42 days (SD = 43.8).
Discussion: Comparison of the quantitative and qualitative results shows
that deviations from the AP have a negative inuence on accessibility and
timeliness.
Conclusions: Regular information to all care providers about the POC
oered and the AP is essential.
Source:
1 Bundesministerium für Gesundheit. Ziele des Nationalen Krebsplans. 2017.
2 Ärztliches Zentrum für Qualität in der Medizin. Qualitätskriterien und Quali-
tätsindikatoren. 2020
Disclosure Statement: e authors declare no conict of interest.
804
Psychological distress in German sarcoma patients—Results
of an large, observational, multicenter Study (PROSa)
Martin Eichler; MSc.1,2; Leopold Hentschel1; Beate Hornemann1;
Stephan Richter2; Susanne Singer3; Peter Hohenberger4; Bernd Kasper5;
Dimosthenis Andreou6,7; Daniel Pink6,8; Karin Arndt9; Martin Bornhäuser1,2;
Jochen Schmitt1,10; Markus K. Schuler2
1National Center for Tumor Diseases (NCT/UCC), University Hospital Dresden
2Clinic and Polyclinic for Internal Medicine I, University Hospital Carl Gustav
Carus
3Institute for Medical Biostatistics, Epidemiology and Informatic, University
Hospital Mainz
4Division of Surgical Oncology & Thoracic Surgery, Mannheim University
Medical Center, University of Heidelberg
5Sarcoma Unit, Mannheim Cancer Center, Mannheim University Medical Center,
University of Heidelberg
6Sarcoma Center Berlin-Brandenburg, Helios Hospital Bad Saarow
7Department of General Orthopedics and Tumor Orthopedics, University
Hospital Münster
8Department of Internal Medicine C, University Hospital Greifswald
9German Sarcoma Foundation
10Center for Evidence-based Healthcare, University Hospital Carl Gustav Carus
Background: Sarcomas are a group of rare, heterogeneous tumors of
mesenchymal origin. Psychological distress diers widely between cancer
types and has rarely been analyzed in sarcoma patients. We aimed to iden-
tify the prevalence of distress in this group and to investigate associated
factors.
Methods: e PROSa (Burden and medical care of sarcoma in Germany)
cohort study was conducted between 2017 and 2020 in 39 German study
centers. For the present analysis, cross-sectional data of adult patients
with sarcoma of any entity were analyzed. Distress was measured with the
Patient Health Questionnaire (PHQ‐4). Associated factors were analyzed
exploratively using multivariable logistic regression models. We included
socio-economical, medical, and patient reported variables with stepwise
backward variable selection.
Result: We included 1095 patients. Prevalence of anxiety was 17.1%,
of depressiveness 19.9%. 26.9% had one or both. In the nal model liv-
ing with children (no vs yes Odds Ratio (OR): 1.6), employment status
(employed vs unemployed OR: 3.3; employed vs disability pension OR:
1.7), fatigue, decreased physical functioning, pain, and time since diag-
nosis (<12month vs. all other) were signicantly associated with distress.
Discussion/ Conclusion: Prevalence of distress is high in sarcoma
patients. With this large observational study, we were able to identify
vulnerable groups for anxiety and depressiveness. Prevalence seems
highest within the rst year aer diagnosis, in patients with low physi-
cal functioning, high fatigue and high pain and in those living in certain
socio-economic conditions (living with children, unemployment, disabil-
ity pension). Clinicians and psycho-oncologist should be aware of these
factors and sensitized for the social aspects of psychological distress.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts210
857
Use of psycho-oncological care after cancer diagnosis –
analysis of inuencing factors
Hannah Reuter1; Jochen Ernst2; Ute Goerling3; Beate Hornemann4;
Anja Mehnert-Theuerkauf2; Tanja Zimmermann1
1Medizinische Hochschule Hannover, Klinik für Psychosomatik und
Psychotherapie, Hannover, Deutschland
2Universitätsklinikum Leipzig, Abteilung für Medizinische Psychologie und
Medizinische Soziologie, Leipzig, Deutschland
3Charité- Universitätsmedizin Berlin, Charité Comprehensive Cancer Center
(CCCC), Berlin, Deutschland
4Uniklinikum Dresden, Nationales Centrum für Tumorerkrankungen, Dresden,
Deutschland
Background: e 2008 National Cancer Plan calls the expansion of psy-
cho-oncological care structures. Given the limited nancial and human
resources and the increasing number of cancer patients, planning of
psycho-oncological care according to the needs becomes increasingly
important. erefore, it is necessary to examine the current status of psy-
cho-oncological care with regard to 1. the use of psycho-oncological care
and 2. the identication of factors inuencing the use, need and demand
of psycho-oncological care. e aim of the study is to identify moderat-
ing factors such as mental distress, socioeconomic status and sociodemo-
graphic aspects, in addition to analyzing actual use, in order to ensure that
psycho-oncological care support is planned in a tailored manner.
Methods: In the longitudinal multicenter study (Leipzig, Berlin, Hanover,
Göttingen, Dresden) ‘LUPE’ (longitudinal analysis of the psycho-onco-
logical demand of patients and their relatives, stratied to biopsychoso-
cial inuencing factors), 1000 patients are surveyed at four measurement
points from diagnosis to follow-up at 6-month intervals. e survey con-
sists of standardized questionnaires and a diagnostic interview (Structured
Clinical Interview for DSM-5). For the present survey, the questionnaire
on mental distress, support needs, and use of psycho-oncological care are
analyzed at the time of the initial measurement.
Result: Initial results are expected by June 2022 and will be presented at
Congress.
Discussion: Signicant dierences in utilization are expected to be found
based on cancer type as well as socioeconomic status and sociodemo-
graphics. Further discussion will be possible with the rst results.
Conclusion: e results of inuencing factors of utilization, need, and
demand should improve the psycho-oncological support structure
Disclosure Statement: e authors declare no conict of interest.
888
Challenges in shared decision-making when prognosis is
limited: development and testing of a decision aid for patients
with advanced lung cancer
Matthias Villalobos-Bollen; Laura Unsöld; Nicole Deis; Anja Siegle;
Michael Thomas
Universitätsklinikum Heidelberg, Thoraxklinik, Internistische Onkologie,
Heidelberg, Deutschland
Introduction: Shared decision-making (SDM) is of increasing impor-
tance in oncology. Decision aids (DA) can help patients to be more
actively involved in the process. ere is still a decit in implementation
in every-day practice and a lack of instruments for specic settings like
advanced cancer with limited prognosis. Patients and health care pro-
viders are challenged by balancing constantly evolving therapeutic algo-
rithms (new treatment options that oen only show marginal benets)
with end-of-life decision-making. erefore, the aim of our study is to
explore and develop specic tools to facilitate the decision-making pro-
cess in metastatic lung cancer.
Methods: Study components include: (1) literature review, (2) semi-struc-
tured guideline-interviews with 9 patients, 6 relatives and 5 health care
professionals (qualitative content analysis following Kuckartz), (3) devel-
opment of DA, (4) feedback from patient support group members (think-
aloud method) and experts, (5) revision and pilot testing.
Results: Review of existing DA for advanced lung cancer showed the lack
of theoretical foundation and reection on personal values. Interviews
revealed that the process of decision-making was mainly characterized by
a lack of perceived options and the missed presentation of “best support-
ive care” (BSC) as an alternative. Our DA was developed using the “con-
ict model of decision-making” (Janis & Mann) and the “four models of
the physician-patient relationship” (Emanuel & Emanuel). Aer feedback
and revision, it includes the topics: information preferences, preferences
in participation, reection on personal values and option-grid including
palliative care. Pilot testing showed acceptance and feasibility.
Conclusions: Being confronted with limited options that only include
active cancer treatment, patients choose a more paternalistic decision
model hazarding the timely integration of palliative care and transition to
BSC. Developing a DA should empower patients to address their personal
values and their preferred role in SDM to achieve goal-concordant care.
Disclosure Statement: e authors declare no conict of interest.
889
Online versus face-to-face – how do video consultations
associate with the doctor-patient-interaction?
Friederike Kendel1; Caren Hilger1; Selamawit Woldai2; Markus Feufel2
1Gender in Medicine, Charité - Universitätsmedizin Berlin, Berlin, Deutschland
2Institut für Arbeitswissenschaft, Technische Universität Berlin, Berlin,
Deutschland
Purpose: Since the corona pandemic, the use of video consultation has
increased markedly. For vulnerable groups such as oncological patients,
the advantages seem obvious. But how, compared to face-to-face con-
sultation, does video consultation potentially change the doctor-patient
relationship? Which barriers may hinder the eective use of this con-
sultation format in practice? We are presenting rst results from a study,
funded by Federal Ministry of Health, which will provide the basis for a
hands-on guide for both physicians and patients on how to improve the
video consultations.
Methods: We use a quasi-experimental mixed-methods design to analyze
qualitative and quantitative dierences between face-to-face and video
consultations. Data collection will be completed by June 2022. We will
record N = 64 videos (n = 32 for each consultation format) with gyneco-
logical and urological cancer patients. Aer the consultation, all patients
answer a questionnaire with questions about their consultation experi-
ence. For quantitative analyses, the counseling sessions will be systemati-
cally compared in terms of verbal and nonverbal communication patterns.
Relative frequencies of eye contact and the information exchanged will be
compared using χ2 -tests. e validated questionnaire MAPPIN’Obsdyad
will be used to assess the quality of shared decision-making parameters. In
addition, semi-structured interviews will be conducted with n = 10 physi-
cians and n = 10 patients experienced with video consultation, for which
a qualitative content analysis will be conducted.
Expected results: We present a complex methodological approach we
used to approach the comparison of video vs. face-to-face consultations.
We will also present rst evidence on how video consultations change the
doctor-patient interaction.
Discussion: We show possible limitations and barriers of video consulta-
tions. Within the framework of a Delphi process, we will use the results to
develop recommendations outlining best practices of video consultations
for both physicians and patients.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 211
961
Navigating the German Health Care System for Financial
Support – Breeding ground for Subjective Distress. A
Qualitative Interview-Study with Cancer Patients in Germany
Andrea Züger1; Viktoria Mathies2; Katja Mehlis1; Sophie Pauge3;
Bastian Surmann3; Luise Richter4; Thomas Ernst2; Wolfgang Greiner3;
Natalja Menold4; Eva Caroline Winkler1
1National Center for Tumor Diseases (NCT), Section of Translational Medical
Ethics, Ethics and Patient oriented Care in Oncology, Heidelberg, Deutschland
2Jena University Hospital, Department of Internal Medicine, Hematology and
Internal Oncology, Jena, Deutschland
3Bielefeld University, School of Public Health, Health Economics and Health Care
Management, Bielefeld, Deutschland
4Dresden University, Institute of Sociology, Methods in Empirical Social
Research, Dresden, Deutschland
Background: A tumor disease can cause high treatment costs and loss
of income. In Germany, a universal healthcare and social welfare system
with dierent providers covers parts of these direct and indirect costs.
However, to obtain payments, patients need to cooperate with health
insurers and social security providers. ese interactions can be frustrat-
ing and exhausting. ere is evidence that bureaucratic burdens nega-
tively aect health outcomes[1]. As a part of a study on nancial eects of
a tumor disease, we investigated patient-reported subjective distress due
to the administrative hurdles they face within the health care system.
Methods: Semi-structured interviews with 18 cancer patients were con-
ducted. Patients were recruited in outpatient (National Tumor Center
Heidelberg) and inpatient (University Hospital Jena) settings. e inter-
views were transcribed verbatim. Qualitative content analysis was used to
identify categories causing subjective distress.
Result: Four categories were identied: extensive eort (1), communica-
tion with providers (2), insucient knowledge and problem of compre-
hension (3), and compulsion to make decisions (4).
Discussion: Financial eects of tumor diseases consist of objective nan-
cial burden (direct and indirect costs) and subjective nancial distress.
Administrative and bureaucratic obligations of patients within the health
care system are strongly associated with both. Obstacles and administra-
tive conicts can limit options of action and result in loss of control, which
in turn results in subjective distress and distrust in the health care system.
Conclusion: Financial eects of tumor diseases in a universal healthcare
setting are multidimensional. In order to better understand and mea-
sure them and develop a patient-reported tool, the bureaucratic burdens
should not be ignored.
Reference:
[1] Herd, P & Moynihan, D. How Administrative Burdens Can Harm
Health, Health Aairs Health Policy Brief; 2020. doi/10.1377/
hpb20200904.405159/full/.
Disclosure Statement: is research is funded by Deutsche Krebshilfe.
996
Together against suicidal ideation and behavior in cancer
patients: The TASC study
Mareike Ernst1; Rüdiger Zwerenz1; Jörg Wiltink1; Elmar Brähler1;
Tamara Schwinn1; Judith Hirschmiller1; Konstantin Strauch2;
Nestor Kapusta3; Manfred E. Beutel1
1Klinik und Poliklinik für Psychosomatische Medizin und Psychotherapie,
Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz,
Deutschland
2Institut für Medizinische Biometrie, Epidemiologie und Informatik,
Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz,
Deutschland
3Universitätsklinik für Psychoanalyse und Psychotherapie, Medizinische
Universität Wien, Wien, Österreich
Background: Cancer can implicate great psychological distress, including
dangerous suicidal ideation and behavior. However, prevalence rates and
risk/protective factors of suicide outcomes in cancer patients and survivors
have hardly been studied in German-speaking countries. Furthermore, it
is currently unclear whether potentially vulnerable patients are adequately
screened by health care providers.
Methods: e project combines analyses of existing data (including a
prospective community cohort and psychotherapeutic intervention stud-
ies) and a new data collection of patients treated at the University Cancer
Center Mainz (UCT Mainz). In total, data from over 24,500 individuals,
among them more than 2,400 cancer patients/survivors, will be used. e
question of whether suicidal ideation in cancer patients is adequately
explored will be investigated using both qualitative (a detailed analysis
of care at the UCT Mainz through interviews with dierent professional
groups) and quantitative methods (a nationwide expert survey).
Result, Discussion, and Conclusion: e project will give insight into
prevalence rates of suicide outcomes in individuals aected by cancer
(according to diagnosis group, time since diagnosis, and compared to
representative population samples). It will also yield in-depth knowledge
of characteristics, psychological and social variables, and behaviors shap-
ing the risk of suicidal crises in the context of cancer, with a focus on
modiable factors that can be addressed by intervention and prevention.
Lastly, it will shed light on potential barriers standing in the way of the
recommended care. Integrating these ndings, the overarching goal is to
contribute to strengthening evidence-based suicide prevention eorts in
cancer patients and survivors.
Disclosure Statement: e authors declare no conict of interest.
1018
Advice and support for lung cancer patients and their
relatives: A randomized controlled trial
Julia Dusel1; Hanna Arnold1; Antonia Rabe2; Horst-Dieter Hummel3;
Pius Jung4
1Julius-Maximilians-Universität Würzburg , Medizinische Fakultät, Würzburg,
Deutschland
2Universitätsklinikum Würzburg, Comprehensive Cancer Center Mainfranken,
Psychoonkologie , Würzburg, Deutschland
3Universitätsklinikum Würzburg, Interdisziplinäres Studienzentrum mit ECTU
CCC Mainfranken, Würzburg, Deutschland
4Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik I -
Pneumologie, Würzburg, Deutschland
Background: e high incidence combined with the high lethality and
bad prognosis highlight the need for psycho-oncological care for patients
as well as their relatives. e primary aim of the study is to investigate the
eects of a more structured care for relatives based on the evidence-based
CALM-Manual (Managing Cancer And Living Meaningfully). In addi-
tion, we investigate to what extent the support of relatives also has an indi-
rect positive eect on patients’ well-being.
Methods: Adult participants regardless of stage of disease or treatment
will be randomly assigned to control-group (CG) or to intervention-group
(IG). Patients as well as their relatives complete assessments at baseline.
Subsequently relatives in the IG receive structured care (3-6 sessions
with psycho-oncologists) and the CG receives standard psycho-oncolog-
ical care. No specic intervention is oered to patients in boths study-
arms, but they can request psycho-oncological support as usual. Patients
as well as relatives receive second assessments post-intervention (IG) or
aer 6 weeks (CG). Assessments examine depression (PHQ-9), anxiety
(GAD-7) and distress (Distress thermometer). Additionally relatives
receive questions about supportive needs (SCNS-SF34-G) and quality of
life (CQOLC). Primary endpoint is a signicant change in GAD-7 of the
IG compared to the CG. Its statistical evaluation is done by a t-test. Power
calculations reveal the need to enroll 88 subjects.
Result: Recruitment is still ongoing. Due to the higher intensity of the
CALM-Intervention, it is expected that the relatives in IG will show greater
improvements in psychological distress and quality of life compared to
those in CG. In addition, the support of the relatives is also presumed to
have an indirect positive impact on patient well-being, depending on its
intensity.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts212
Discussion: If an eect can be demonstrated, this can help improve care
for the target group.
Disclosure Statement: e authors declare no conict of interest.
1030
App-based psycho-oncological support for cancer patients to
improve distress – a randomized controlled trial
Franziska Springer1; Ayline Maier2; Michael Friedrich1; Jan Simon Raue2;
Gandolf Finke2; Anja Mehnert-Theuerkauf1
1University Medical Center Leipzig, Medizinische Psychologie und Medizinische
Soziologie, Leipzig, Deutschland
2Fosanis Gmbh, Berlin, Deutschland
Background: Cancer patients oen suer from high levels of distress, but
access to psycho-oncological support is scarce, especially in rural areas.
erefore, digital psycho-oncological support, such as the app “Mika” by
Fosanis GmbH, oers immediate and permanently accessible support
for cancer patients. e aim of the study was to investigate the ecacy of
Mika on general distress.
Methods: Cancer patients of all types of tumors (³18 years) were recruited
online via Social Media ads and at the Leipzig medical center. In an RCT,
the intervention group (IG, N=99) received immediate access to the app,
whereas the wait list control group (CG, N=119) received access aer
12-weeks. Primary outcome was general distress, measures with the
NCCN distress thermometer. All outcomes were assessed online at base-
line, 2, 6 and 12 weeks. We applied intention-to-treat (ITT) and per-pro-
tocol analysis (PP), i.e., completion of all questionnaires, no app use in the
CG, compliant app use in the IG. Analysis of covariance was used to assess
the change from baseline to 12-weeks between groups.
Result: e mean age of the patients was 56 years, 61% were female. e
most frequent cancer types were breast cancer (34%) and hematological
cancer (28%). e drop-out rate was 16%. e analysis included 218 and
166 patients for ITT and PP, respectively. Both analyses revealed a sig-
nicant improvement of general distress in the IG, compared to the CG.
Eect sizes were small and classied as clinically relevant by a minimal
important dierence analysis.
Discussion and Conclusion: Mika is an eective app-based support
program for cancer patients to reduce general distress with eect sizes
comparable to other psycho-oncological interventions, such as psycho-
education or psychotherapy. However, there is scare literature on compa-
rable digital psycho-oncological support programs. Mika is a promising
opportunity to provide additional support to cancer patients during their
disease and therapy.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
1057
Preliminary results on the feasibility and eectiveness of the
emotion-based psycho-oncological online self-help epos
Angeliki Tsiouris1; Anna Mayer1; Jörg Wiltink1; Christian Ruckes2;
Manfred E. Beutel1; Rüdiger Zwerenz1
1Universitätsmedizin Mainz, Klinik und Poliklinik für Psychosomatische Medizin
und Psychotherapie, Mainz, Deutschland
2Interdisziplinäres Zentrum Klinische Studien (IZKS) Mainz, Mainz, Deutschland
Background: Internet-based interventions are considered as a promising
oer for cancer patients to improve their psychological well-being and
overcome existing barriers to seeking psycho-social support. While exist-
ing psycho-oncological online interventions have primarily used behav-
ioral and mindfulness-based approaches, psychodynamic approaches
are underrepresented. With the online self-help program epos, the rst
German-language psycho-oncological online self-help program based on
psychodynamic concepts has been developed. e aim of the study is to
evaluate the feasibility and eectiveness of epos in reducing psychological
distress in people with cancer.
Methods: N=327 people with cancer participated in the randomized
controlled trial. Participants in the intervention group had access to the
online self-help program epos for 10 weeks, while participants in the
control group received treatment as usual and access to an informational
website. Participants completed questionnaires at three time points (T0
baseline, T1 post-intervention, T2 follow-up). An analysis of covariance
will be used to test the hypothesis of whether participants in the interven-
tion group report lower scores in psychological distress, measured by the
PHQ-ADS, at the end of the intervention period compared to participants
in the control group. Secondary outcomes include anxiety and depressive
symptoms, quality of life, emotion control, and posttraumatic growth.
Result: By the time of the congress, data collection and analyses will be
completed, allowing the presentation of preliminary results on the feasi-
bility and eectiveness of epos.
Discussion: e study results will be discussed with regard to limitations
and strengths of the study design.
Conclusion: As the rst German-language psycho-oncological online
self-help with a psychodynamic focus, epos might complement conven-
tional psycho-oncological treatment oers and contribute to the diversity
of psychotherapeutic orientations in the digital context.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 213
Quality-of-Life
Best-of-Abstract-Vortrag
358
Change towards a healthier lifestyle is associated with better
health-related quality of lifein long-term colorectal cancer
survivors
Ruth Elisa Eyl1,2; Melissa Thong3; Prudence Carr1; Lina Jansen1;
Jenny Chang-Claude4,5; Michael Homeister1; Hermann Brenner1,6,7;
Volker Arndt3
1Deutsches Krebsforschungszentrum, Abteilung Klinische Epidemiologie und
Alternsforschung, Heidelberg, Deutschland
2Klinikum Stuttgart, Stuttgart Cancer Center – Tumorzentrum Eva Mayr-Stihl,
Stuttgart, Deutschland
3Deutsches Krebsforschungszentrum, Cancer Survivorship, Heidelberg,
Deutschland
4Deutsches Krebsforschungszentrum, Genetic Epidemiology, Heidelberg,
Deutschland
5University Medical Center Hamburg-Eppendorf, University Cancer Center
Hamburg (UCCH), Cancer Epidemiology Group, Hamburg, Deutschland
6Deutsches Krebsforschungszentrum, Division of Preventive Oncology,
Heidelberg, Deutschland
7Deutsches Krebsforschungszentrum, German Cancer Consortium, Heidelberg,
Deutschland
Background: Lifestyle factors are important in tertiary prevention for col-
orectal cancer (CRC) survivors. To date, a few cross-sectional studies have
studied a combination of lifestyle factors and health-related quality of life
(HRQOL). Further, no study has investigated whether a change towards
a healthier lifestyle is positively associated with HRQOL in CRC survi-
vors years aer diagnosis. erefore, our study aimed to assess whether a
change in a combination of lifestyle factors was associated with HRQOL
up to 10 years post-diagnosis.
Methods: We used data from the prospective population-based DACHS
study for 2283 CRC survivors. A healthy lifestyle score (HLS) previously
developed by our research group was adopted. e HLS, derived from
ve modiable lifestyle factors (smoking, alcohol consumption, diet, body
fatness, and physical activity), were assessed at diagnosis, 5-year (5YFU),
and 10-year follow-up (10YFU). HRQOL was assessed by the EORTC
Quality of Life Questionnaire-Core 30 at 5YFU and 10YFU. Multivariable
linear regression and linear mixed models were used to explore associa-
tions between changes in the survivors´ lifestyle and HRQOL over time.
Results: Survivors who improved their HLS from baseline to 5YFU
reported better functioning, higher global health/QOL and less com-
plaints of fatigue and dyspnea at 5YFU than survivors who maintained
a high HLS from baseline to 5YFU. In longitudinal analyses, survivors
with an improved HLS reported better functioning during follow-ups,
although physical functioning decreased over time regardless of HLS.
Survivors with improved HLS reported generally less complaints with
fatigue, pain and dyspnea during follow-ups, in comparison to the groups
who maintained a low or decreased HLS.
Discussion: A change towards a healthier lifestyle was associated with
better functioning and less symptom burden.
Conclusion: Our results reinforce the importance of tertiary prevention
through the support of maintaining or promoting a healthier lifestyle
among long-term CRC survivors.
Disclosure Statement: e authors declare no conict of interest.
946
Longitudinal course of global health-related quality of life
and fatigue up to 5 years after radiotherapy in an
international multicentre observational cohort of men with
prostate cancer
Petra Seibold1; Miguel E Aguado Barrera2; David Azria3; Erik Briers4;
Renée Bultjinck5; Alessandro Cicchetti6; Ananya Choudhury7;
Sara Gutiérrez-Enríquez8; Thomas Heger1; Irmgard Helmbold1;
Rudolf Kaaks1; Maarten Lambrecht9; Tim Rattay10; Barry S Rosenstein11;
Dirk De Ruysscher12; Elena Sperk13; Hilary Stobart14; R Paul Symonds10;
Christopher J Talbot10; Riccardo Valdagni6,15; Ana Vega2; LIV Veldeman5;
Tim Ward14; Adam Webb10; Catharine ML West7; Jenny Chang-Claude1,16;
Tiziana Rancati6
1German Cancer Research Center (DKFZ), Heidelberg, Deutschland
2Fundacion Publica Galega Medicina Xenomica, Santiago de Compostela,
Spanien
3ICM Institut du Cancer Montpellier, Montpellier, Frankreich
4Belgien
5Ghent University Hospital, Ghent, Belgien
6Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italien
7The University of Manchester, Manchester, Vereinigtes Königreich
8Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spanien
9UZ Leuven, Leuven, Belgien
10University of Leicester, Leicester, Vereinigtes Königreich
11Mount Sinai School of Medicine, New York, USA
12Maastro Clinic, Maastricht, Niederlande
13Universitätsmedizin Mannheim, Mannheim, Deutschland
14Vereinigtes Königreich
15University of Milan, Milan, Italien
16University Medical Center Hamburg-Eppendorf, Hamburg, Deutschland
Background: To prospectively assess the course of health-related quality
of life (HRQoL) and fatigue in a multicentre cohort of men with prostate
cancer (PCa) up to ve years aer radiotherapy (RT).
Methods: Adult men with non-metastatic PCa were recruited 2014-2016
prior to start of RT (external beam and/or brachytherapy according to
local standard of care; +/- hormonal treatment [HT], +/- prostatectomy)
into the multicentre international observational REQUITE study (www.
requite.eu). Data on HRQoL was prospectively collected using EORTC
QLQ C30 at multiple time points between pre-RT baseline (BL, N=1,714)
and 5 years aer RT (N=496). So far, 1,495 men completed at least one
post-RT survey 2-5 years aer RT. Global health status/QoL and the
fatigue domain were analysed.
Result: Global HRQoL scores declined from mean scores of 74.9 at BL to
69.9 at the end of RT. One year aer RT, the mean scores returned to BL
levels and remained stable until 5 years. Fatigue levels peaked at the end
of RT (26.6 vs. 17.3 at BL) and returned to BL levels aerwards. Fatigue
scores varied signicantly by country. Patients with HT reported higher
mean fatigue levels than patients without (p<0.05, BL through 2 years).
Severe fatigue (i.e. above the threshold for clinical importance of >=39;
PMID: 31639445) was reported by 11%, 23%, 15%, and 11% of the men
at BL, end of RT, at 2 years and at 5 years, respectively. 25% and 35% of
men experienced a deterioration of HRQoL or fatigue (change of >= 10;
median age of 70/71, respectively, vs. 68 without deterioration), respec-
tively, when comparing 5-year scores to BL.
Discussion: e long-term follow-up is still ongoing (RADprecise/
REQUITEplus projects) and multivariate models accounting for rele-
vant co-variates using updated data will be presented at the congress and
will identify the impact of treatment versus general health related factors
including age.
Conclusion: Despite good overall HRQoL, long-term survivorship care
for men with PCa should routinely include patient reported outcome mea-
sures as an important tool to identify unmet health needs (e.g. fatigue).
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts214
Poster
20
Feasibility and safety of exercise with patients suering
from advanced pancreatobiliary cancers(aPBC) receiving
beyond rst-line chemotherapy with and without exercise
therapy (P-Move)
Nico De Lazzari1; Miriam Götte2; Freerk T. Baumann3; Timo Niels3;
Martin Schuler1,4; Jörg Hense1; Stefan Kasper-Virchow1; Mitra Tewes1,
Jens Siveke1,4,5
1Universitätsklinikum Essen, Westdeutsches Tumor Zentrum, Innere Klinik
(Tumorforschung), Essen, Deutschland
2Universitätsklinikum Essen, Zentrum für Kinder- und Jugendmedizin,
Kinderheilkunde III, Essen, Deutschland
3CIO - Centrum für Integrierte Onkologie Uniklinik Köln, Köln, Deutschland
4Deutsches Konsortium für Translationale Krebsforschung (DKTK),
Partnerstandort Universitätsklinikum Essen, Essen, Deutschland
5Institut für Experimentelle Tumortherapie, Westdeutsches Tumorzentrum,
Essen, Deutschland
Background: Patients (Pts) with advanced pancreatobiliary cancers
(aPBC) frequently suer from high symptom burden. Studies of curative
treatments indicate that exercise can reduce treatment side eects and
improve patient-related outcomes (PROMs). However, evidence from
prospective studies in the palliative settings is rare. e primary aim of
the prospective, randomized-controlled study P-MOVE is to evaluate the
feasibility of exercise therapy (ET) in patients with aPBC beyond rst-line
chemotherapy.
Methods: 40 Pt (Stage III/IV) will be recruited beyond rst-line therapy.
Pts are randomized according to the minimization procedure with strata:
gender, age and loss of body weight past six months. e intervention
group (IG) completes 3 training units per week for 8 weeks (1x super-
vised strength training, 2x individualized home-based trainings weekly).
Control group (CG) receives recommendations on daily activities.
Result: Since study initiation, 158 Pts were screened. Of those 126 Pts
did not meet eligibility criteria. Of 32 eligible Pts, 22 have been recruited
(68.7%). Reasons for not participating were distance to study center
(n=5), clinical deterioration or death during screening period (n=3) and
no interest in ET (n=2). e drop-out rate was 31.8% (4 in IG and 3 in C).
Main reasons for drop-out were reduced general condition due to disease
progression (n=5) and cancer-related death (n=1). Adherence to ET in
total was 132/168 (78.5%) and 86/112 (76.7%) for unsupervised ET ses-
sions. No adverse events related to ET were reported. Statistical compari-
son of PROMs will be provided with higher patient enrolment.
Discussion: Pts with aPBC are highly motivated to ET aer rst-line
chemotherapy but suer from high symptom burden. Drop-out rates are
comparable to other clinical trials studying ET in palliative cancer treat-
ment settings. Supervised ET oered twice weekly may be more ecient
to improve PROMs.
Conclusion: Preliminary data suggest that ET beyond rst-line palliative
treatment in Pts with aPBC appears feasible and safe yet challenging.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
23
Patient-reported outcome measurement (PROM) of the
health-related quality of life of patients with supercial
urothelial carcinoma of the urinary bladder
Desiree Louise Dräger; Benedikt Kunz; Laila Schneidewind;
Julia Nolting; Oliver Hakenberg
Klinik und Poliklinik für Urologie, Universitätsmedizin Rostock, Rostock,
Deutschland
Purpose: Bladder carcinoma is the second most common tumor dis-
ease in urology. e supercial variant is characterized by a high rate of
recurrence, so that close follow-up care is necessary, which inuences the
quality of life. A supplementary module to the EORTC-QLQ-C30, the
QLQ-NMIBC-24, is currently available for examining the health-related
quality of life (QoL) in supercial bladder cancer. e aim of the study
was to measure the patient-reported outcome of the QoL of patients with
supercial bladder carcinoma.
Material: Evaluation of patients with supercial bladder cancer (n = 141)
using EORTC-QLQ-C30 and -QLQ-NMIBC-24. ese provide informa-
tion about quality of life, functional scales (physical, emotional, cognitive,
social functioning and role function), general symptom scales, 6 individ-
ual items (including inappetence, insomnia) and cancer-specic function
and symptom scales (including voiding, sexuality).
Results: e examined patients showed poor emotional, social and role
function. ey also reported more frequent loss of appetite, fatigue,
insomnia and voiding problems. Patients who received intravesical instil-
lation therapy showed a poorer health-related QoL than patients without
intravesical relapse prevention.
Discussion: Patients with supercial bladder cancer have an impaired
quality of life. e so-called "response shi" must be taken into account,
which leads to shis within the function and symptom scales with con-
stant QoL, i.e. the priorities are rearranged with a time lag to the surgery.
Conclusions: e reduced quality of life in patients with supercial blad-
der cancer must be considered in the follow-up care by the attending phy-
sician and alternative solutions must be oered if necessary.
Disclosure Statement: e authors declare no conict of interest.
232
Severity of postprostatectomy urinary incontinence and
quality of life
Marc Heydenreich; Dirk-Henrik Zermann
Vogtland-Klinik Bad Elster, Bad Elster, Deutschland
Background: Postoperative urinary incontinence has major eects on
psychosocial health. e aim of the study was to examine what inuence
the early continence situation has on the health-related quality of life
(QoL) of patients aer radical prostatectomy.
Methods: 92 patients (Ø 64.0 years) aer radical prostatectomy took
part in the study. e health-related Quality of life (FACT-G) and pros-
tate-specic functional restrictions (FACT-P) were assed using a ques-
tionnaire (Functional Assessment of Cancer erapy) at the beginning of
a follow-up rehabilitation (mean - 14.8 days p.o.). e severity of urinary
incontinence was evaluated with the 1-hour pad test.
Result: severity of urinary incontinence <=10g (n=50):
physical well-being=24.1 (3.6); functionality=19.4 (5.1); FACT-P=32.9
(5.6); mental well-being=19.9 (3.3)
severity of urinary incontinence >=11g (n=42):
physical well-being=22.5 (3.3); functionality=18.4 (5.4); FACT-P=29.1
(6.7); mental well-being=20.2 (3.3)
p-value within the group aer 21 days of rehabilitation:
physical well-being=0.03; functionality=0.69; FACT-P=0.003; mental
well-being=0.35
Discussion: ere are signicant QoL dierences in physical well-being
and in FACT-P between low and higher amounts of urine loss.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 215
Conclusion: e study results show that the health-related quality of life
(physical well-being, FACT-P questionnaire) is negatively inuenced in
patients with greater urine loss (> 50g / 1-h pad test). Accordingly, in
addition to therapeutic treatment of urinary incontinence, these patients
should receive urological advice and psychological support.
Disclosure Statement: e authors declare no conict of interest.
288
Inuence of side eects of therapy on quality of life and
treatment satisfaction of gynecological cancer patients in
BNGO practices in Germany in 2020
Jörg Schilling; Beatrice Schröder; Petra Ortner
BNGO e.V., Neuenhagen, Deutschland
Background: To ensure the quality of outpatient care for patients (pts.)
with gynecological malignancies in BNGO practices and to evaluate the
quality of life of the patients and physical and psychosocial burden and
stress caused by the therapy, the BNGO has been conducting surveys
among patients who are cared for in BNGO practices since 2012. e last
survey took place from February to July 2020.
Methods: e NCCN distress thermometer was used by the patients to
evaluate the general stress caused by the therapy in the past week. e fre-
quency of symptoms and side eects during therapy as well as long-term
side eects and the use of complementary measures were documented
in patient diaries. Side eects and stress caused by chemotherapy in the
patients who received chemotherapy were recorded separately.
Results: By February 2021, 1,853 patient questionnaires have been
returned from 46 practices e most common problems and those per-
ceived as most stressful by all patients irrespective of therapy modality
were sleep disorders, followed by tiredness/exhaustion, numbness/tin-
gling in the extremities and bone and muscle pain. Alopecia was a signif-
icant problem in chemotherapy patients and was much distressing for the
respective patients.
Discussion: Sleeping disorders, fatigue, exhaustion and bone and muscle
pain were the most distressing side eects in all patients independently of
therapy mode. Alopecia, peripheral neuropathy and nausea were the most
distressing side eects in chemotherapy patients.
Conclusion: Like in the last surveys, the patients were highly satised
with the treatment in BNGO practices. Overall, 98% of patients would
choose outpatient treatment again and 99.5% would return to the same
practice.
Disclosure Statement: e authors declare no conict of interest.
299
Study Protocol of a Randomized Controlled Trial:
Argentine Tango for Breast Cancer Patients with Fatigue
Shiao Li Oei1; Anja Thronicke1; Thomas Rieser2; Sarah Becker3;
Jessica Groß3; Harald Matthes1,4,5; Friedemann Schad1,5
1Forschungsinstitut Havelhöhe gGmbH am Gemeinschaftskrankenhaus
Havelhöhe, Berlin, Deutschland
2Charite-Universitätsmedizin Berlin, corporate member of Freie Universität
Berlin and Humboldt-Universität zu Berlin, Institut für Sozialmedizin,
Epidemiologie und Gesundheitsökonomie, Berlin, Deutschland
3Gemeinschaftskrankenhaus Havelhöhe Frauenheilkunde und Geburtshilfe,
Brustkrebszentrum, Berlin, Deutschland
4Medical Clinic for Gastroenterology, Infectiology and Rheumatology CBF,
Charite-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin
and Humboldt-Universität zu Berlin, Institut für Sozialmedizin, Epidemiologie
und Gesundheitsökonomie, Berlin, Deutschland
5Gemeinschaftskrankenhaus Havelhöhe Interdisziplinäre Onkologie und
Palliativmedizin, Berlin, Deutschland
Background: Many breast cancer patients suer from persistent impair-
ment, particularly cancer-related fatigue (CRF), which severely impacts
their quality of life. e purpose of this study is to investigate whether a six
week tango module is suited as a therapeutic approach for breast cancer
patients to favorably inuence their quality of life, especially fatigue levels.
Methods: Sixty breast cancer patients with fatigue, diagnosed 12-48
months before enrollment with cancer stage I-III are recruited and ran-
domized 1:1 to a tango or a waiting-list group. Movement concepts using
elements of Argentine tango, which are oriented towards walking in music,
self- and spatial perceptions are examined with the participants during
six weekly 60 min tango sessions. e primary outcome is the improve-
ment of fatigue (German version of the Cancer Fatigue Scale). Secondary
outcomes are the improvement in sleep quality (Pittsburgh Sleep Quality
Index) and quality of life (EORTC-QLQ-C30). Patient reported outcomes
are measured at baseline and six weeks later and an evaluation will be
performed by means of descriptive data analysis.
Result: It is anticipated that aer the six-week tango module CRF, sleep
and quality of life scores will improve. First results will be presented.
Discussion: To counter fatigue symptoms, exercise and physical activity
are recommended as rst-line interventions, and mind-body and music
therapies have also been shown to be eective in reducing stress. Tango
therapy that combines various elements may therefore have benecial
eects in breast cancer patients.
Conclusion: It is expected that physical, psychological, and cognitive
skills could be supported with Argentine tango in breast cancer patients.
A follow-up evaluation will reveal how this tango module is perceived by
the participants and how lasting the eects will prove to be.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
456
Introducing SKINFO – the new and unique web-based
information platform for German-speaking skin cancer
patients
Theresa Steeb1; Julia Homann2; Friedegund Meier2; Christiane Weber3;
Maike Bergmann2; Anne Müller-Schuchardt2; Nina Weiler4;
Astrid Doppler5; Carola Berking1; Dirk Schadendorf6
1Hautklinik, Universitätsklinikum Erlangen, Erlangen, Deutschland
2Klinik und Poliklinik für Dermatologie, Universitätsklinikum Carl Gustav Carus
Dresden, Dresden, Deutschland
3MEDEA GmbH Medical Education Academy, Saarbrücken, Deutschland
4Eurice - European Research and Project Oce GmbH, Sankt Ingbert,
Deutschland
5Melanom Info Deutschland - MID e.V., Essen, Deutschland
6Universitätsklinikum Essen Hautklinik, Essen, Deutschland
Background: e incidence of skin cancer has been rising steadily for
years. An increasing need for reliable information has been observed
among patients, as being informed about the disease is an integral part for
informed decision-making. e Internet represents the most important
source to acquire disease-related information. However, web-based infor-
mation for skin cancer patients was previously found to be of insucient
quality.
Methods: An interdisciplinary team of dermato-oncologists, health care
scientists, patient representatives and communication experts developed
the website in a multi-step process. Following this, usability tests were
conducted to identify problems and to optimize the websites rst dra.
Importantly, the content of the website as well as externally available
sources (videos, brochures) will be continuously reviewed by all relevant
stakeholders using evidence-based criteria, i.e. medical experts will check
the correctness, health care scientists the reliability and patient represen-
tatives evaluate the relevance.
Result: SKINFO (www.infoportal-hautkrebs.de) has been launched in
02/21 and addresses German-speaking skin cancer patients, their relatives
and interested parties. e website provides high quality and reviewed
information on common and less common skin cancer entities as well as
information on further patient-related topics, i.e. psychosocial support,
nance or lifestyle. Usability testing revealed that the websites layout, nav-
igation and content need optimization.
Discussion: SKINFO is the rst web-based platform including common
and less common skin cancer entities and relevant topics with high qual-
ity and reviewed information. Physicians may recommend SKINFO as it
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts216
represents an easily accessible, up-to-date and reliable source of informa-
tion. Further usability tests will be performed in order to optimize the
website.
Conclusion: e unique web-based information platform has the poten-
tial to enable patients and their relatives to cope with skin cancer and thus,
strengthen informed decision-making.
Disclosure Statement: e authors declare the following:
Honorare für Vorträge und Beratertätigkeiten
471
Perspectives and concerns of German women with an
increased hereditary risk for breast and ovarian cancer
regarding infection-specic risks and cancer-specic risks
during the SARS-CoV-2 pandemic: Results of a cross-sectional
web-based survey
Roxana Schwab; Annika Droste; Annette Hasenburg
University Medical Center Mainz, Department of Gynecology and Obstetrics,
Mainz, Deutschland
Background: e SARS-CoV-2 pandemic has aected the entire world,
but some subgroups of patients have been disproportionally aected.
Cancer patients showed a higher prevalence of COVID-19 disease, as well
as a higher incidence of severe COVID-19 illness and higher death rates
from COVID-19.
Methods: To assess the perspectives and believes of women with an
increased hereditary risk for breast (BC) and ovarian (OC) cancer regard-
ing infection-specic and cancer-specic risks during the SARS-CoV-2
pandemic, a web-based survey was placed on internet platforms of sup-
port groups between 29th January and 22th April 2021. Data are presented
as frequencies of selected items. Correlations were assessed by non-
parametric tests.
Result: Asked about their concerns to face a more severe disease course
of COVID-19 illness, 44.2% responded, they were not concerned, while
27.3% were more concerned and 23.4% were signicantly more con-
cerned. Higher concerns were correlated with higher age (p=0.001) and
were associated with a positive history of invasive breast cancer (p=0.001).
When asked about concerns of being at higher risk for occurrence of
breast and ovarian cancer aer being infected with SARS-CoV-2, 72.7%
reported no concerns, while 11.7% reported moderate concerns and 5.2%
had signicant concerns. Higher concerns were correlated with higher age
(p<0.047), while higher resilience was a protective factor (p=0.029)
ose with a positive medical history for in situ or invasive BC or OC were
asked about concerns regarding an unfavorable oncological outcome as a
result of an infection with SARS-CoV-2. 23.0% had no concerns, while
24.3% had moderate increased concerns and 14.9% reported signicantly
increased concerns.
Discussion: Age proved to be a risk factor for health-related worries
during the COVID-19 pandemic, while higher resilience proved to be
protective to health-related concerns.
Conclusion: Patients with additional risk factors may be at risk to experi-
ence health-related worries and anxiety, and should be monitored closely.
Disclosure Statement: e authors declare the following:
RS: Honoraria: Roche Pharma AG, AstraZeneca, Streamedup!GmbH, AH: Hono-
raria: AstraZeneca; Celgen; MedConcept GmbH, Med update GmbH; Medicultus;
Pzer; Promedicis GmbH; Soconsult; Roche Pharma AG; Streamedup!GmbH;
Tesaro Bio Germany GmbH, LEO Pharma
532
Clinical and sociodemographic determinants of disease-
specic health-related quality of life in long-term breast
cancer survivors
Daniela Doege1; Melissa Thong1; Lena Koch-Gallenkamp2; Heike Bertram3;
Andrea Eberle4; Bernd Holleczek5; Alice Nennecke6; Ron Pritzkuleit7;
Annika Waldmann8; Sylke Ruth Zeissig9; Hermann Brenner2,10,11;
VolkerArndt1
1German Cancer Research Center (DKFZ), Division of Clinical Epidemiology and
Aging Research, Cancer Survivorship, Heidelberg, Deutschland
2German Cancer Research Center (DKFZ), Division of Clinical Epidemiology and
Aging Research, Heidelberg, Deutschland
3Cancer Registry of North Rhine-Westphalia, Bochum, Deutschland
4Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen
Cancer Registry, Bremen, Deutschland
5Saarland Cancer Registry, Saarbrücken, Deutschland
6Hamburg Cancer Registry, Hamburg, Deutschland
7Cancer Registry of Schleswig-Holstein, Lübeck, Deutschland
8University Lübeck, Institute of Social Medicine and Epidemiology, Lübeck,
Deutschland
9Cancer Registry of Rhineland-Palatinate, Mainz, Deutschland
10German Cancer Research Center (DKFZ), Division of Preventive Oncology,
Heidelberg, Deutschland
11German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK),
Heidelberg, Deutschland
Background: It is important to monitor disease-specic issues of breast
cancer survivors (BCS) to be aware of potential unmet supportive care
needs. Most studies on disease-specic health-related quality of life
(HRQoL) in BCS had small samples, low cancer stages, or limited to
short-term survivors, certain age ranges or treatments. Our study aims
to address gaps of previous studies, by using a large, population-based
cohort of long-term BCS (5-15 years post-diagnosis), including a broad
range of ages, stages and treatments.
Methods: e sample of 3045 BCS (age 30-89 years) was recruited
in a German multi-regional population-based study (CAESAR+).
Disease-specic HRQoL was assessed by the European Organization
for Research and Treatment of Cancer Breast Cancer-Specic Quality of
Life Questionnaire (EORTC QLQ-BR23). Dierences in HRQoL were
assessed with multiple regression, adjusted for age, education, time since
diagnosis, stage, recurrence, and self-reported treatments (operation, che-
motherapy, endocrine therapy, radiotherapy, lymph node dissection).
Result: Body image and future perspective increased with age, whereas
sexual functioning decreased with age. At 30-49 years, women who had
breast-conserving therapy or mastectomy with breast reconstruction (BR)
reported a better body image compared to those who had mastectomy
alone. At 50-79 years, there was no dierence according to mastectomy
with/without BR. In specic age groups, lymph node dissection and radio-
therapy were associated with arm and breast symptoms, and chemo- and
endocrine therapy were associated with worries about hair loss. Disease-
free BCS aged 30-79 years reported a better future perspective than those
who reported any metastasis, recurrence or second cancer.
Discussion: Disease-specic HRQoL in long-term BCS was mainly
age-dependent. Nevertheless, in some subgroups, treatment-associated
symptoms were found long aer diagnosis.
Conclusion: Vulnerable BCS should be monitored longitudinally.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 217
617
Evaluationofthe 12-week exercise interventionYOUEX on
quality of life and fatigue inyoung adults with cancer
Annelie Voland1,2; Miriam Götte3; Verena Krell4; Maximilian Köppel1,2;
Timo Niels5; Inaam El-Rajab1,2; Joachim Wiskemann1,2
1Nationales Centrum für Tumorerkrankungen – NCT, Heidelberg, Deutschland
2Universitätsklinikum Heidelberg, Heidelberg, Deutschland
3Universitätsmedizin Essen, Zentrum für Kinder- und Jugendmedizin, Essen,
Deutschland
4Charité - Universitätsmedizin Berlin, Abteilung Sportmedizin, Berlin,
Deutschland
5Uniklinik Köln, Centrum für Integrierte Onkologie (CIO) Köln, Köln, Deutschland
Background:Anoverwhelming body of scientic evidencedisplays the
positive eects of physical activity for cancer patients.However, infor-
mation about the ecacy of digital exercise programs to ameliorate
tumor-therapy-relatedside eectssuch as cancer related fatigue (CRF)
and health related quality of life (QoL)for young adults with cancer is
scarce.
Objective:e aim of this study is to analyze the impact of a 12-week
exercise interventionon CRF andtheQoLin young cancer patients (18–
39 years).
Methods: We recruited patients who currently have or had a cancer
diagnosis within the past 5 years.Eligible patients chosebetween three
exercise modules (M1: social mediaexercise program, M2: independent
training via online-training platform, M3: participation in an in-per-
son community-based exercise program).e selected modulecouldbe
replaced or amended by another module aer 6weeks.Primary endpoints
were assessed by questionnaires (EORTC QLQ-C30 and QLQ-FA12)
atthreetime points (T0: baseline, T1: aer 6 weeks intervention; T2: aer
12 weeks intervention).
Results: Within 8 months n=105 participants were recruited, and n=92
started the intervention. Mean age was 31.9 (± 4.85) years, 93.4% were
female, and 55.43% had a breast cancer diagnosis. Quality of life scales
physical functioning, social functioning, and emotional functioning
improved signicantly from baseline to T2 (all p<0.01), but global quality
of life did not change (56.8; 58.2). Fatigue, as measured with the QLQ-
C30 symptom scale signicantly improved from baseline to T2 (59.8;
50.4, p<0.0001), but not in the three fatigue scales as measured with the
QLQ-FA12.
Discussion:Global quality of life and fatigue as measured with the FA12
were reduced in the YOUEX group but did not change from baseline
to post-intervention. Although the study is lacking a control group, the
intervention seems to be eective to improve the functional dimensions
of quality of life.
Conclusion:Due to the discrepant results on fatigue, no clear statements
can be made on this at present and further analyses are required.
Disclosure Statement: e authors declare no conict of interest.
635
Development of tumor disease-specic PRO-CTCAE item sets
Maximilian Günther1; Theresa Müller2; Markus Schuler3,4;
Leopold Hentschel2; Katharina Schütte3; Yon-Dschun Ko5;
Ingo Schmidt-Wolf6; Ulrich Jaehde1
1Institute of Pharmacy, Clinical Pharmacy, University of Bonn, Bonn,
Deutschland
2University Cancer Centre (NCT/UCC), University Hospital Carl Gustav Carus
Dresden, Psychooncology, Dresden, Deutschland
3University Cancer Centre (NCT/UCC), University Hospital Carl Gustav Carus
Dresden, Dresden, Deutschland
4Onkologischer Schwerpunkt, Oskar-Helene-Heim Berlin, Berlin, Deutschland
5Department of Internal Medicine, Johanniter Hospital Bonn, Internistische
Onkologie, Bonn, Deutschland
6Department of Integrated Oncology, University Hospital Bonn, Bonn,
Deutschland
Background: In oncology, adverse events (AE) are documented using the
Common Terminology Criteria for Adverse Events (CTCAE)1. is phy-
sicians-reported assessment can be supported by patient-reported out-
comes (PRO)2. For this reason, the NCI has developed a PRO version of
the CTCAE criteria, consisting of a pool of 78 symptoms and 124 items3.
A core item set containing 31 items for patients with chemotherapy has
already been validated in German4.
e aim of this study was to develop tumor disease-specic PRO-
CTCAE item sets for dierent tumor entities with high content validity.
Methods: Patients treated at three outpatient centres were asked to assess
the occurrence and relevance of the 78 PRO-CTCAE symptoms using
a questionnaire. In order to select PRO-CTCAE items for each tumor
entity, individual symptoms were ranked on the basis of occurrence and
relevance.
Result: 101 patients with breast cancer (BC), 107 with multiple myeloma
(MM) and 66 with prostate cancer (PC) were analysed. e BC item set
contains 21 symptoms, the MM and PC item set each 19 symptoms. 8
symptoms are included in all three item sets. e symptoms with the
highest rankings across the item sets were fatigue and sleep disorders.
Symptoms with the highest rankings included only in one item set were
symptoms aecting the urogenital system in the PC item set, blurred
vision in the BC item set and appetite loss in the MM item set.
Conclusion and Outlook: Based on patient-reported dierences in symp-
tom pattern, specic PRO-CTCAE item sets with high content validity
were developed for BC, MM and PC. In order to validate the quality and
psychometric criteria of the new item sets further studies are required.
e validation of the PRO-CTCAE-MM item set is currently ongoing in
a multicentre, one-time survey using a browser-based app. Within the
survey patients complete the PRO-CTCAE-MM item set and the corre-
sponding EORTC questionnaires.
Indication of source:
1 NCI. CTCAE Version 5.0. 2017
2 Basch E. N Engl J Med 2010; 362: 865-869
3 Basch E et al. J Natl Cancer Inst 2014; 106: 1-11
4 Hagelstein V et al. Ann Oncol 2016; 27: 2294-2299
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts218
898
Prognostic potential of baseline HRQoL in advanced and
metastatic renal cell carcinoma
Viktor Grünwald1; Peter J. Goebell2; Martin Schostak3; Manfred Welslau4;
Christian Doehn5; Elisa Degenkolbe6; Rainer Ehneß6; Kerstin Ahrens7;
Martin Bögemann8
1Universitätsklinikum Essen, Westdeutsches Tumorzentrum Essen, Innere Klinik
(Tumorforschung) und Klinik für Urologie, Essen, Deutschland
2Universitätsklinikum Erlangen, Urologische Klinik, Erlangen, Deutschland
3Otto-von-Guericke-Universität Magdeburg, Klinik für Urologie, Uroonkologie,
Robotergestützte und fokale Therapie, Magdeburg, Deutschland
4Klinikum Aschaenburg-Alzenau, Hämato-Onkologische Schwerpunktpraxis,
Aschaenburg, Deutschland
5Urologikum Lübeck, Lübeck, Deutschland
6Novartis Pharma GmbH, Novartis Oncology, Nuernberg, Deutschland
7APOGEPHA Arzneimittel GmbH, Dresden, Deutschland
8Universitätsklinikum Münster, Klinik für Urologie und Kinderurologie, Münster,
Deutschland
Combinations of laboratory and clinical parameters complement each
other to risk scores such as IMDC. Well-established prognostic factors are
needed to predict patient’s outcome. e prognostic value of health-re-
lated quality of life (HRQoL) has been shown for various tumor entities.
Here, we report baseline QoL-values and their prognostic potential for
renal cell carcinoma (RCC) patients.
In the prospective, non-interventional PAZOREAL study, 376 RCC
patients were treated with pazopanib in rst line and other antineoplastic
agents (i.e., nivolumab, everolimus), subsequently. HRQoL was evaluated
with ve-dimensional EuroQol EQ-5D-5L questionnaire in 279 patients.
Five dimensions comprising mobility, self-care, usual activities, pain/dis-
comfort and anxiety/depression are rated by a 5-digit-scale. Out of this,
a single value index called baseline utility score (BUS) was calculated
non-parametrically. Self-rated health was reported by visual analogue
scale (VAS) at baseline. Both, VAS and BUS, were categorized into four
subgroups: poor, low-intermediate (med-low), high-intermediate (med-
high) and good according to its quartiles.
e median VAS at baseline was 70 with lower (25%) and upper (75%)
quartiles at 50 and 80, respectively. Median BUS was 0.9 with quartiles at
0.716 and 0.918. Median overall survival (mOS) diered in the subgroups
between 14.7 months (poor), 30.1 months (med-low), 48.3 months (med-
high) and 53.6 months (good). For patients with poor BUS, mOS was 14.8
months, whereas mOS for med-low, med-high and poor BUS was 53.6,
43.4 and 41.5 months, respectively. Linear regression analysis of OS with
each score revealed a signicant correlation with R=0.22.
Addition of baseline HRQoL might improve prognostic tools to pre-
dict RCC patients outcome. However, only one score should be consid-
ered for further analysis. Although correlation of OS with VAS or BUS is
comparably low, VAS tends to separate dened subgroups more precisely.
us, our data indicate that VAS score is more suitable as additional prog-
nostic marker in RCC patients.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
905
Patient needs and wishes in cancer therapy - online survey
with cancer patients
Beke Freyer1; Helen Beckmann2; Christine Blome1
1Institut für Versorgungsforschung (IVDP), Hamburg, Deutschland
2AstraZeneca GmbH, Wedel, Deutschland
Background: Cancer impacts patients’ quality of life (QoL) severely.
erefore, it is important to include the patients’ perspective in cancer
research and treatment. is study aimed to analyze patients’ view on
their cancer therapy and the evaluation of their recovery.
Methods: 248 participants with dierent cancer types (mainly breast,
prostate, lung and ovarian) lled in online questionnaires in 2020. Most
questions were quantitative, covering the topics QoL, cancer recovery and
the patients’ view on their therapy. Several qualitative questions covered
topics such as feeling recovered. e quantitative results were analyzed
with descriptive methods using IBM SPSS Statistics, the qualitative results
were coded with inductive categories.
Result: e mean age of patients was 60.9 years, 61.7% were female
(n=153). Most participants had undergone surgery as a treatment for their
cancer (n=204), 147 patients had received radiation therapy and 122 had
received chemotherapy.
In the therapy, the most important aspect for patients was the best
possible QoL, followed by longest possible survival; having longest pos-
sible therapy free period was the least important aspect in all subgroups.
Most patients felt well involved in therapy decisions; men reported they
had been presented with more options by their doctor than women.
Chances of recovery were overall rated as rather good (arithmetic mean of
5.61; Likert-scale 1 to 7). Reasons why patients did not yet feel recovered
included the physical impact of the cancer, the fear to experience a relapse,
and others.
Discussion: Having the best possible QoL seems to be the most import-
ant aspect in cancer therapy for patients. Even though patients mostly
received only one therapy option by their doctor, they feel well involved
in the therapy decisions.
However, due to the heterogeneity of the population and the small sample
size of subgroups, results have to be interpreted with caution.
Conclusion: e patient perspective is crucial and needs to be included
in the cancer treatment planning as the QoL is the most important aspect
during the therapy.
Disclosure Statement: e authors declare the following:
Projekt gesponsert von AstraZeneca GmbH
909
Prostate Cancer Patient Reported Outcome After Cyberknife
Robotic Radiosurgery
Sebastian Exner; Felix Behrens; Fabian Fehlauer
1Strahlenzentrum Hamburg MVZ, Hamburg, Deutschland
Background: e optimal management of localized Prostate Cancer (PC)
should take account consideration of patient and clinical risk factors. e
objectives of this cohort study of men with newly diagnosed localised PC
were to document side eects with the International Prostate Symptom
Score (IPSS), International Consultation on Incontinence Questionnaire
Short Form (ICIQ-SF), International Index of Erectile Function
Questionnaire (IIEF-5) and as well Patient-Reported Outcomes version
of the Common Terminology Criteria for Adverse Events Questionnaire
(PRO-CTCAE) following radiosurgery with the Cyberknife.
Methods: In this cohort analysis, 40 patients with localized PC were
analyzed who received Cyberknife radiosurgery (5 x 7,25 Gy) and com-
pleted the IPSS, ICIQ-SF, IIEF-5 and the German validated PRO-CTCAE
questionnaires.
Result: Mean IPSS score was 6.9 (mild symptomatic), mean ICIQ-SF score
was 3.3 (mild impairment of incontinence), mean IIEF-5 score was 17.0
(mild erectile dysfunction). e highest score at PRO-CTCAE was for
urinate frequency (two patients, 5%), achieve and maintain erection (two
patients, 5%), ejaculation problems (four patients, 10%) and decreased
libido (two patients, 5%). ere was no signicant dierence at follow-up
period or treated prostate volume (F/U: > 1 vs. < 1 year; Volume ml: >64
vs. <64). Local control and overall survival were 100%.
Discussion: e local control of the radiosurgery was with longer fol-
low-up periods persistently very high with low toxicity. In particular, the
late toxicity appears to be lower than with surgery or conventional exter-
nal radiation. Since curative therapy options in man with localized PC
remain iso- eective, it is important to choose a treatment strategy with a
low impact on the health-related quality of life and high cure rate.
Conclusion: Radiosurgery for localized PC shows good local control and
overall survival with a very mild side eect reported by patients.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 219
968
Improved quality of life (QOL) with lisocabtagene
maraleucel (liso-cel), a CD19-directed chimeric antigen
receptor T cell therapy, compared with standard of care (SOC)
using salvage chemotherapy (CT) followed by autologous
stem cell transplantation (ASCT) as second-line (2L) treatment
in patients (pt) with relapsed or refractory (R/R) large B-cell
lymphoma (LBCL): results from the phase 3 TRANSFORM study
Bertram Glaß1; Jeremy Abramson2; Patrick B Johnston3; Manali Kamdar4;
Sami Ibrahimi5; Koji Izutsu6; Jon Arnason7; Pim Mutsaers8;
Matthew Lunning9; Julia Braverman10; Fei Fei Liu10; Alessandro Crotta11;
Sandrine Montheard11; Alessandro Previtali11; Shien Guo12;
Ling Shi12; Scott Solomon13
1Helios Klinikum Berlin-Buch, Berlin, Deutschland
2Massachusetts General Hospital Cancer Center, Massachusetts, USA
3Mayo Clinic, Jacksonville, USA
4University of Colorado Cancer Center, Colorado, USA
5University of Oklahoma Stephenson Cancer Center, Oklahoma, USA
6National Cancer Center Hospital, Tokyo, Japan
7Beth Israel Deaconess Medical Center, Boston, USA
8Erasmus University Medical Center, Rotterdam, Niederlande
9University of Nebraska Medical Center, Omaha, USA
10Bristol Myers Squibb, New York, USA
11Celgene, a Bristol-Myers Squibb Company, Zürich, Schweiz
12Evidera, Seattle, USA
13Northside Hospital Cancer Institute, Atlanta, USA
Background: Pts with previously treated R/R LBCL have compromised
health-related QOL (HRQOL). Here we present pt-reported outcomes
(PRO) from TRANSFORM.
Methods: TRANSFORM is a pivotal, randomized, phase 3 study compar-
ing liso-cel vs SOC (3 cycles of salvage CT then ASCT in responders) in
adults (18–75 y) with R/R LBCL ≤ 12 mo aer rst-line therapy intended
for ASCT. Crossover to liso-cel was allowed in the SOC arm. e EORTC
QLQ-C30 and FACT-LymS were administered at randomization (baseline
[BL]) and on Day (D) 29 (liso-cel infusion or 2 cycles of salvage CT), 64
(1 mo aer liso-cel or CT completion), and 126 (3 mo aer liso-cel or 2
mo aer ASCT), and at Mo 6. No PRO data were collected aer crossover.
Global health/QOL (GH/QOL), physical functioning, cognitive function-
ing, fatigue, pain, and FACT-LymS were the primary domains of inter-
est. Prespecied thresholds dened clinically meaningful score changes.
A linear mixed model for repeated measures (MMRM) analysis assessed
dierences in least squares (LS) mean change from BL up to D126. All
analyses were descriptive.
Result: Of 184 randomized pts, 90 (49%) and 85 (46%) pts, respec-
tively, completed the EORTC QLQ-C30 (liso-cel vs SOC, n = 47 vs 43)
and FACT-LymS (n = 45 vs 40). In MMRM analyses, liso-cel tended
toward more favorable overall LS mean changes up to D126 vs SOC in
most domains. In particular, dierences in cognitive functioning (2.21
vs −2.09) and fatigue (−1.95 vs 3.75) for liso-cel vs SOC, respectively,
exceeded prespecied minimal important dierence thresholds. In indi-
vidual-level analyses, the proportions with meaningful deterioration in
fatigue and GH/QOL were lower for liso-cel vs SOC from BL to Mo 6.
At Mo 6, a lower proportion had worsened fatigue (18% vs 71%) and a
higher proportion had improved fatigue (47% vs 29%) for liso-cel vs SOC;
for GH/QOL, a lower proportion worsened (18% vs 57%) and a higher
proportion improved (53% vs 14%), respectively.
Discussion: Most primary HRQOL domains were more favorable in
liso-cel- vs SOC-treated pts.
Conclusion: ese data support use of liso-cel as 2L therapy in pts with
R/R LBCL.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
1049
Geruchs- und Geschmacksveränderungen beeinträchtigen
Krebspatienten mit Chemotherapie – eine prospektive
longitudinale nicht-interventionelle Studie
Tobias Bleumer1; Clara Kalweit1; Wolfgang Böhmerle2,3; Thomas Hummel4;
Sebastian Stintzing1; Lars Uwe Stephan1; Uwe Pelzer1
1Department of Hematology, Oncology and Tumorimmunology, Charité
Campus Mitte, Charité -Universitätsmedizin Berlin, Corporate Member of Freie
Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health,
Berlin, Deutschland
2Department of Neurology, Charité Campus Mitte, Charité - Universitätsmedizin
Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu
Berlin, and Berlin Institute of Health, Berlin, Deutschland
3Charité - Universitätsmedizin Berlin, corporate member of Freie Universität
Berlin and Humboldt Universität zu Berlin, NeuroCure Cluster of Excellence,
Berlin, Deutschland
4Department of Otorhinolaryngology, Smell and Taste Clinic, Technische
Universität Dresden, Dresden, Deutschland
Introduction: Taste and smell alterations (TSA) are common side eects
in cancer patients undergoing chemotherapy. However, the connection
between specic malignancies and their corresponding chemotherapeutic
substances with TSA remains unclear. Also, longitudinal investigations
of TSA with both subjective and objective methods are scarce. e aim
of this study is to investigate TSA and its eects on cancer pts regarding
anorexia, weight loss, reduced quality of life (QOL) and the possible asso-
ciation with neuropathy.
Methods: Patients starting palliative or curative chemotherapy will be
surveyed and examined up to ve times (T0-T4). As of March 31, 2022,
50 out of 100 patients have been investigated. Clinical assessment is con-
ducted using psychophysical methods (Snin’ Stick and Taste Strips),
questionnaires, and electrophysiological examination. Development
of TSA and correlation with clinical and sociodemographic parame-
ters were analyzed using the Friedman-Test, Mann-Whitney-U-Test, or
Spearman-Correlation.
Results: Olfactory and gustatory function dropped 18.2% and 22.4%
between baseline and T1 ( p= 0.003 for both). ere was no signicant
TSA between T1 and T2, however (p= 0.377 and p= 0.45). Although poly-
neuropathy scores increased signicantly between T0 and T2 (p= 0.005),
the Mann-Whitney-U test only showed a tendency in relationship to
TSA so far (p= 0.095). Further analyses showed signicantly greater BMI
reduction and loss of appetite in patients experiencing stronger olfactory
dysfunction between T0 and T1 (p= 0.04 andp= 0.02, respectively). No
signicant changes were shown when grouped by gustatory dysfunction.
Full recruitment is expected in September 2022.
Conclusion: is rst set of data shows the extensive eect of TSA in
cancer patients undergoing chemotherapy. Aer analyzing the complete
data set, we dene dependencies between TSA, specic entity and therapy
more precisely in order to discuss therapeutic consequences and possible
prevention strategies, which will then form the basis for interventional
follow-up studies.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts220
Radiation
Best-of-Abstract-Vortrag
522
First analysis of the phase IV studyTARGIT B(oost) Q(uality)
R(egistry) using intraoperative radiotherapy as anticipated
boost in breast cancer patients
Elena Sperk1; Christel Weiss2; Robert Schnaubelt3; Uta Kraus-
Tiefenbacher4; Viktoria Brück5; Lelia Bauer6; Stefan Dinges7;
Albert von der Assen8; Christina Kaiser9; Heidrun Meye10;
Benjamin Tuschy11; Sebastian Berlit11; Marc Sütterlin11; Michael Ehmann1;
Ahmed Yasser Abou-Madian1; Katharina Fleckenstein1; Frank Schneider1;
Sven Clausen1; Frederik Wenz12
1Universität Heidelberg, Universitätsmedizin Mannheim, Medizinische Fakultät
Mannheim, Klinik für Strahlentherapie und Radioonkologie, Mannheim,
Deutschland
2Universität Heidelberg, Universitätsmedizin Mannheim, Medizinische Fakultät
Mannheim, Biostatistik, Mannheim, Deutschland
3Lukaskrankenhaus Neuss GmbH, Medizinisches Versorgungszentrum, Neuss,
Deutschland
4Krankenhaus Nordwest, Radioonkologie, Frankfurt am Main, Deutschland
5Asklepios Klinik Barmbek, Brustzentrum, Hamburg, Deutschland
6GRN-Klinik Weinheim, Brustzentrum, Weinheim, Deutschland
7Städtisches Klinikum Lüneburg gemeinnützige GmbH, Klinik für
Strahlentherapie und Radioonkologie, Lüneburg, Deutschland
8Niels-Stensen-Kliniken Franziskus-Hospital Harderberg , Brustzentrum,
Georgsmarienhütte, Deutschland
9Universitätsfrauenklinik Bonn, Abteilung für Senologie/zertiziertes
Brustzentrum, Bonn, Deutschland
10Gesundheit NordhessenMVZ, Fachbereich Strahlentherapie, Kassel,
Deutschland
11Universität Heidelberg, Universitätsmedizin Mannheim, Medizinische Fakultät
Mannheim, Frauenklinik, Mannheim, Deutschland
12Uniklinik Freiburg, Freiburg im Breisgau, Deutschland
Background: TARGIT BQR is a prospective multicenter phase IV study
to evaluate clinical outcome aer intraoperative radiotherapy (IORT) with
low kV x-rays used as an anticipated boost in combination with a standard
external beam radiotherapy of the whole breast (EBRT) in high-risk breast
cancer patients in a real world setting.
Methods: IORT was given immediately aer tumor resection with median
20 Gy in 1 fraction. Median RT time was 24 minutes. Median interval
between IORT and EBRT was 36 days. EBRT and systemic treatment
were given according to local standard/S3 recommendations. e study
was approved by the local Ethics Committee (2011-319N-MA) and is reg-
istered in clinicaltrials.gov (NCT01440010). All patients gave informed
consent. Statistical analyses were done with SAS, release 9.4.
Result: In total, 1133 patients from 10 centers in Germany were included
into the registry with 20.4% screening failure/drop out/missing data. IORT
boost was done in 90% and EBRT in 96%. Median FU was 32 months (1–
120) and median age 61 years (26–90). Risk factors were seen as follows:
22% N+, 23% >T1, 78% G2/3, 12% L1, 1% V1, 3% R1 and 10% Her2neu+.
Chemotherapy was given in 35% and 87% received endocrine therapy.
Postoperative erythema appeared in 4.9% and 10.7% had palpable seroma
with 0.4% requiring puncture. Wound healing disorder occurred in 2.3%.
Local recurrence occurred in 10 cases aer 12-55 months. Ipsi-/contralat-
eral tumor occurred in 2 and 3 patients aer 55 - 66 and 26-86 months,
respectively and metastasis in 14 cases aer 9-102 months. Overall 16 of
902 patients with at least 1 month FU (1.8%) died.
Discussion: is is the largest prospective data set with IORT as a boost
with low kV x-rays showing rst results with excellent clinical outcome.
Detailed toxicity data will be shown during presentation. Our data con-
rm previous retrospective single center analyses in a multicenter real
world setting in Germany.
Conclusion: IORT as a boost is a feasible method with excellent clinical
outcome.
Disclosure Statement: e authors declare no conict of interest.
584
Prophylactic cranial irradiation in extensive disease small cell
lung cancer
David Alexander Ziegler; Sonia Ziegler; Leif Hendrik Dröge; Martin Leu;
Sandra Donath; Manuel Guhlich; Markus Anton Schirmer;
Stefan Rieken
Universitätsmedizin Göttingen, Klinik und Poliklinik für Strahlentherapie
und Radioonkologie, Göttingen,
Background: e prot of prophylactic cranial irradiation (PCI) in
patients with extensive disease small cell lung cancer (ED-SCLC) is a con-
troversial topic. We performed a retrospective analysis of 89 patients in
order to evaluate the inuence of PCI on overall survival (OS).
Methods: Using data of our clinical information systems SAP, ixserv, ARIA
and oncostar we identied patients tagged as “SCLC” and “small cell lung
cancer”. All patients were included, who underwent radiation therapy
(RT) of at least one site except for brain metastases. Chi-squared test was
used to compare ECOG-status and rate of bone metastases between two
cohorts. Overall survival was calculated with Kaplan Meier estimator. e
signicance of the prognostic factors was veried with the log-rank test.
Result: Between 2007 and 2017, 89 patients with ED-SCLC with-
out brain metastases received RT in our institution. 63 of the 89
patients (70.8%) received PCI with fractionations of 10-15 x 2-3 Gy,
26 patients did not receive PCI. Mean age was 63.5 years in both
cohorts. In the PCI cohort, 25 patients (39.7%) were additionally
irradiated for pulmonary sites, 20 patients (31.8%) received addi-
tional bone irradiation. Within the patients without PCI, 13 patients
(50%) received thoracic RT and 17 patients (65.4%) bone RT.
ECOG-status was signicantly worse in patients without PCI. e rate of
bone RT diered signicantly between both cohorts. Mean OS was signi-
cantly better in the PCI cohort (6.8 months vs. 3.2 months).
Discussion: Patients with ED-SCLC without brain metastases receiving
PCI showed signicantly improved OS compared to patients without PCI.
In this retrospective study, ECOG-status and rate of RT of bone metasta-
ses were unbalanced, a selection bias cannot be excluded.
Conclusion: PCI in ED-SCLC leads to improved OS. Further prospective
studies are needed to verify these ndings.
Indication of source:
1 Ziegler, D. A., et al. DEGRO Jahrestagung 2021
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 221
Poster
34
Neoadjuvant chemoradiotherapy of cervical carcinoma
Leif Hendrik Dröge1; Manuel Guhlich1; Markus Schirmer1;
Laura Anna Fischer1; Sonia Ziegler1; David Alexander Ziegler1;
Stefan Rieken1; Stephanie Bendrich1
1Klinik und Poliklinik für Strahlentherapie und Radioonkologie,
Universitätsmedizin Göttingen (UMG), Göttingen, Deutschland
S Donath1; LH Dröge1; M Guhlich1; M Schirmer 1; LA Fischer1; A Ziegler1;
S Ziegler1; S Rieken1; S Bendrich1
1Universitätsmedizin Göttingen, Klinik für Strahlentherapie und
Radioonkologie, Robert-Koch-Straße 4037075 Göttingen
Background: Chemoradiotherapy (CRTx) is an integral part of the mul-
timodal treatment of patients with cervical carcinoma. However, done
postoperatively it leads to signicant toxicity due to high dose exposure
of bladder and bowel. In the context of a clinical series we investigated
the dose-reduced neoadjuvant CRTx in 40 patients with high-risk cervical
carcinoma at the University Hospital of Göttingen.
Methods: 40 patients (mean age 49 yrs, range: 26-74) with high-risk
cervical cancer were treated preoperatively between 2005 and 2018.
Normofractionated RT was delivered over 5 weeks with mean doses of
45 Gy in combination with cisplatin weekly. Patients underwent surgery
within 4-6 weeks aer their last radiotherapy. Data collection was per-
formed using hospital-owned soware (SAP, Aria, iXserv, and Onkostar),
and statistical analysis was performed using Statistika (ethical approval
33/6/21).
Results: Out of 40 patients, 39 underwent surgery and therefore 98% of
the patients were treated per protocol, taking into account good compati-
bility and high compliance. Clinically relevant downstaging was achieved
in 90% of patients. One patient died 5 months aer surgery, the patient
who refused surgery died 74 months aer last RT without any further
therapy. Overall survival rates aer 1, 5 and 10 years were 93, 86 and 70%,
respectively.
Discussion: Dose-reduced neoadjuvant CRTx leads to high response
rates and does not impede surgery. High survival rates were achieved with
moderate acute toxicities, such as low grade cystitis and enterocolitis.
Conclusion: We here present an innovative neoadjuvant treatment
approach for patients with borderline resectable cervical cancer, in whom
impressive rates of response to preoperative CRTx at modest rates of
perioperative and long term toxicities were observed.
Disclosure Statement: e authors declare no conict of interest.
36
Outcome and toxicity of image-guided boost irradiation in
patients with relapsed prostate cancer after surgery
Fabian Schunn1; Stephan Mende1; Ingmar Schlampp1; Jonas Ristau1;
Anna Kraemer1; Tanja Eichkorn1; Andreas Kudak1; Tim Holland-Letz2;
Klaus Herfarth1; Jürgen Peter Debus1; Stefan A. Koerber1
1Universitätsklinikum Heidelberg, Radioonkologie und Strahlentherapie,
Heidelberg, Deutschland
2Deutsches Krebsforschungszentrum, Heidelberg, Deutschland
Background: Salvage-radiotherapy (SRT) is a common treatment option
in prostate cancer patients with biochemical failure aer primary pros-
tatectomy. It can be performed with simultaneously integrated boost
(SIB) to PSMA-PET-positive lesion, if respective imaging is available at
the time of planning. However, the signicance of SIB during SRT is not
well understood. is study aimed to describe adverse eects (AE) under
SIB-SRT and compared biochemical progression-free survival (bPFS) and
overall survival (OS) between SIB-SRT and regular SRT.
Methods: We reviewed radiation data of patients with biochemical
relapse aer initial prostatectomy, treated with SRT +/- SIB at Heidelberg
University Hospital from 01/2005 to 07/2019. We compared rates of bPFS
and OS as primary endpoints, utilizing the cox model. Secondary end-
point was the descriptive analysis of AE before, under and aer SIB-RT,
following CTCAE version 4 criteria.
Results: A total of 85 patients (23 SIB-SRT, 62 SRT) were eligible for anal-
ysis, median follow-up was 21 months. Patients mostly ranked high-risk
following DAmico scoring (77,1%, n=64). SIB-SRT showed hazard ratios
of 0.43 (CI: 0,09 – 2,18) for bPFS and 0.08 (CI: 0,03 – 1,83) for OS, p-val-
ues were not signicant. During SIB-SRT no grade IV and only one grade
III AE (urinary congestion) were observed. All patients reported °I-II AE,
most commonly nycturia and diarrhea.
Discussion: A benecial eect of SIB on bPFS and especially OS can
be assumed, however, results were not statistically signicant. SIB-SRT
showed low AE in most patients with improvement 6-8 weeks aer treat-
ment. Limitations of this study are its retrospective approach and small
sample size.
Conclusion: We conclude that SIB-SRT is safe with occurrence of mostly
low grade genitourinary and gastrointestinal AE. Rates of bPFS and OS
were higher in patients with SIB to PSMA-PET-positive lesions, however a
signicant eect could not be demonstrated. A prospective approach and
greater sample size could help to evaluate the signicance of SIB during
SRT.
Disclosure Statement: e authors declare no conict of interest.
191
Oncologic therapy support via means of a dedicated mobile
app – a prospective feasibility evaluation (OPTIMISE-1)
Fabian Schunn1; Rami El Shae2; Andreas Kudak1; Dorothea Kronsteiner1;
Nina Bougatf1; Anna Krämer1; Sebastian Regnery1; Timo Machmer3;
Jürgen Peter Debus1; Nils Henrik Nicolay4
1Universitätsklinikum Heidelberg, Radioonkologie und Strahlentherapie,
Heidelberg, Deutschland
2Universitätsmedizin Göttingen, Strahlentherapie und Radioonkologie,
Göttingen, Deutschland
3Karlsruher Institut für Technologie, Karlsruhe, Deutschland
4Universitätsklinikum Freiburg, Freiburg im Breisgau, Deutschland
Background: Mobile health (m-health) is gaining interest, with mobile
devices being ever more available among medical facilities and patients.
We aimed to examine the feasibility of app-based treatment surveillance
in patients undergoing radiotherapy (RT). Next to technical practicability
and acceptance, we assessed patient satisfaction and quality of life under
treatment.
Methods: is prospective single-center study was performed at
Heidelberg University Hospital between 08/18 - 01/20. During RT we
measured patients’ quality of life (QoL), symptoms and treatment satis-
faction. Respective questionnaires (EORTC QLQ-C30 + diagnose spe-
cic modules, RAND PSQ-18) were presented to patients via a mobile
app, running on a designated tablet device. e primary endpoint was
determined by the fraction of patients, who completed at least 80% of
items. Secondary endpoints were disease-related quality of life and patient
satisfaction.
Result: 49 cancer patients (14 breast, 13 pelvic, 12 bronchial, 10 prostate)
were eligible for analysis. 79,6% [95%-CI: 66.4-88.5%] (n=39) completed
at least 80% of items received by mobile app. A mean of 227,5 +/- 48,25
questions were answered per patient. Breast cancer patients showed the
highest rate of answered questions, with 92,9% (n=13) completing at least
80% of items. QoL and patient satisfaction are reported visually.
Discussion: Patients showed high acceptance with 79,6% (n=39) com-
pleting at least 80% of the given items. Strengths of this study are the pro-
spective approach with a designated app as well as the usage of validated
measurement tools. Limitations are the single-center design and sample
size.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts222
Conclusion: e use of a mobile app for reporting symptoms and QoL
under RT is feasible and well accepted by patients. It may allow for
resource-ecient, detailed feedback to the medical sta and assist in the
assessment of side eects over time. Further interest lies in the develop-
ment of new measurement tools, specically designed for this task.
Disclosure Statement: e authors declare no conict of interest.
227
Radiochemotherapy for locally advanced non-small cell
lung cancer (NSCLC) in patients staged with PET/CT scan vs.
conventional staging: A comparison of treatment patterns,
treatment compliance, and outcomes
Julian Muster; Felix-Nikolai Oschinka Jegor Habermann;
Alexander Ziegler; Sonia Ziegler; Laura Anna Fischer; Andrea Hille;
NiklasJosua Alt; Stephanie Bendrich; Sandra Donath;
Markus Anton Schirmer; Manuel Guhlich; Rami El Shae;
Stefan Rieken; Martin Leu; Leif Hendrik Dröge
University Medical Center Göttingen, Department of Radiotherapy and
Radiation Oncology, Göttingen, Deutschland
Background: In the multicenter PET-Plan trial, a PET/CT based target
volume reduction in denitive radiochemotherapy (RCT) for locally
advanced NSCLC was demonstrated to be safe and eective. We compared
results aer treatment based on PET/CT scan vs. conventional staging.
Methods: A total of 273 patients were included. We compared baseline
and radiotherapy characteristics, treatment compliance, and survival
(Cox regression analysis) between patients who received a PET/CT scan
before treatment (n=170, 62.2%) and patients who underwent conven-
tional staging (n=103, 37.8%).
Result: Patients with PET/CT scan had lower T stages (T1-2, 35.8% vs.
22.3% for conventional staging, p=0.02). Moreover, patients presented
with PET/scan more frequently in the period from 12/2013 to 12/2019
(n=120/137 (87.6%) vs. n=50/136 (36.8%) in the period from 01/2008
to 11/2013, p<0.01). Patients with PET/CT scan received ≥80% of the
planned radiotherapy dose more oen (93.5% vs. 82.5% of the patients
with conventional staging, p<0.01). In multivariable analysis, staging with
PET/CT scan (HR=0.61), age <65 years (HR=0.67), and Karnofsky index
≥90% (HR=0.67) were associated with better overall survival (p<0.05).
Discussion: e lower T stages in patients with PET/CT scan possibly
reect that, when compared to conventional staging, patients with T3-4
tumors were less frequently referred to RCT due to the detection of distant
metastases. PET/CT scan improved the compliance with RT and was asso-
ciated with better patient survival in a similar way like basic parameters
(age, Karnofsky index).
Conclusion: e increasing number of patients with PET/CT scan in the
recent period reects that PET/CT scans were already integrated into clin-
ical practice to a relevant extent. Our results highlight the utmost impor-
tance of PET/CT scans for an adequate patient selection and an eective
treatment in the context of curative RCT. As stated by the investigators of
the PET-Plan trial, a PET/CT scan before RCT should be standard of care.
Disclosure Statement: e authors declare no conict of interest.
234
Postoperative radiotherapy or sequential radiochemotherapy
in the curative treatment of women with uterine sarcoma
Eva Meixner1,2,3; Laila König1,2,3; Andreas Kudak1; Kristin Lang1,2,3;
Jürgen Peter Debus1,2,3,4 5; Juliane Hörner-Rieber1,2,3
1Abteilung für RadioOnkologie und Strahlentherapie, Universitätsklinikum
Heidelberg, Heidelberg, Deutschland
2Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Deutschland
3National Center for Tumor diseases (NCT), Heidelberg, Deutschland
4German Cancer Research Center (DKFZ), Clinical Cooperation Unit Radiation
Oncology, Heidelberg, Deutschland
5Heidelberg Ion Therapy Center (HIT), Heidelberg, Deutschland
Background: Women with uterine sarcoma represent a rare heteroge-
nous group with low unproven evidence regarding the optimal adjuvant
treatment. e aim was to evaluate outcome, toxicity and the impact
of prognostic factors for postoperative radiotherapy (RT) or sequential
radiochemotherapy (RCHT) aer hysterectomy.
Methods: We retrospectively identied 51 patients at the Department of
Radiation Oncology at the University Hospital of Heidelberg, treated with
adjuvant RT or RCHT for carcinosarcomas (CS, n=30), leiomyosarcoma
(LMS, n=14) and endometrial stromal sarcoma (ESS, n=7) between 2001-
2021. All patients were treated with external beam pelvic RT (median
EQD2: 64.4Gy, range: 43.2-80.4Gy), a vaginal surface brachytherapy boost
was added in 40 patients (median boost dose: 10Gy, range: 5-20Gy)
Results: With a median follow-up of 34.7 months, overall survival (OS)
was 89.9%, 73.3% and 51.7% and distant progression free-survival (dPFS)
was 84.0%, 72.3% and 60.7% for 1-, 2- and 5-years, respectively. Local
control (LC) rates for 1- and 5-years were 93.7% and 88.2%. In univariate
Cox analysis, LC was inferior with a higher FIGO stage (p=0.038), posi-
tive resection margins (p=0.013) and serosal involvement (p=0.042) and
interestingly, OS was superior with a shorter time interval from surgery
to start of RT (p=0.047). Multivariate Cox analysis identied higher age
(p=0.044), positive resection margin (p=0.041) and cervical inltration
(p=0.002) as independent prognostic factors for inferior OS. Only moder-
ate toxicity was observed with no high-grade toxicity (CTCAE grade ≥ 4).
Discussion: During the period under review, aliation for CS has
changed towards endometrial carcinoma. Nonetheless, CS, LMS and ESS
suered from extremly poor prognosis, with the vast majority due to dis-
tant failures.
Conclusion: is study conrms the poor OS of women with uterine
sarcoma with high failures in distant control. Radiotherapy shortly aer
hysterectomy appears to be safe and well tolerated achieving ecient
promising LC for this aggresssive, high-risk tumor entity.
Disclosure Statement: e authors declare no conict of interest.
244
Dosimetric comparison of combined pulmonary Stereotactic
Radiotherapy (SBRT) and mediastinal conventionally
fractionated Volumetric Arc Therapy (VMAT) versus
conventionally fractionated VMAT only in advanced stage
Non-Small Cell Lung Cancer (NSCLC)
Tanja Eichkorn1; Cedric Stüwe1; Eric Tonndorf-Martini1; Kai Schubert1;
Sebastian Regnery1; Thomas Held1; Farastuk Bozorgmehr2;
Petros Christopoulos2; Laila König1; Patrick Naumann1;
Sebastian Adeberg1; Klaus Herfarth1; Michael Thomas2; Stefan Rieken3;
Jürgen Peter Debus1; Rami El Shae3
1Department of Radiation Oncology, Heidelberg University Hospital,
Heidelberg, Deutschland
2Thoracic Clinic, Heidelberg University Hospital, Heidelberg, Deutschland
3Department of Radiation Oncology, Göttingen University Hospital, Göttingen,
Deutschland
Background: In radiotherapy planning of inoperable advanced stage
Non-Small Cell Lung Cancer (NSCLC), dose to the lungs can be a limit-
ing factor, especially in case of a peripherally located primary. erefore,
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 223
we evaluated whether normofractionated irradiation of the mediasti-
nal lymph nodes (MLN) combined with stereotactic body radiotherapy
(SBRT) for the primary can achieve a more favorable dose distribution in
the surrounding lung tissue, compared to conventionally fractionated RT
of MLN and primary as a combined target volume.
Methods: Comparative radiotherapy plans were calculated for 21 patients
with inoperable advanced stage NSCLC, extensive metastatic MLN and a
peripherally located primary, as described above. Volumetric modulated
arc therapy (VMAT) technique was used for both SBRT and convention-
ally fractionated RT.
Result: Target volume was smaller with the combined conventional
RT and SBRT approach than with the conventional RT only approach
(median volume [ml]: 307 vs. 441, p=0.0001). Also, low-dose lung expo-
sure (median V5Gy [%]: 71.2 vs. 77.0, p=0.00002) and low-dose heart
exposure (median V5Gy [%]: 40.6 vs. 48.9, p=0.0006) were signicantly
reduced with the combined conventional RT and SBRT approach. ere
was no dierence observed in dose exposure of esophagus and spinal cord.
In this selected cohort, conventional irradiation of primary and MLN in a
single target volume resulted in clinically unacceptable dose exposure of
the lungs necessitating dose reductions or unacceptably impaired target
volume coverage. Clinical data on toxicity and tumor control follow.
Discussion: Irradiated lung volume and dose exposure of organs at risk
was signicantly lower with this tissue-sparing than the conventional
radiotherapy approach.
Conclusion: In cases with peripherally located primary, the combination
of SBRT for the primary and fractionated RT for MLN is dosimetrically
feasible and can provide an alternative to dose reductions necessitated by
otherwise very large target volumes.
Disclosure Statement: e authors declare no conict of interest.
557
Extent of resection margin for oral cavity squamous cell
carcinoma undergoing postoperative radiotherapy: what is an
adequate margin?
Kristin Lang
Universitätsklinik Heidelberg, Radioonkologie, Heidelberg, Deutschland
Background: When adequate resection in patients with oral cavity
squamous cell carcinoma (OCSCC) is attained, no adjuvant treatment
is needed; however, re-resection or radiotherapy may be indicated for
patients with positive margins or in case of extracapsular extension of
lymph nodes. e aim of this study was to examine the clinical signi-
cance and impact of surgical margins size in patients with OCSCC under-
going adjuvant radiotherapy.
Methods: We included 162 patients with OCSCC in this retrospective
study, who underwent postoperative radiotherapy between 2000 and 2019
at the Department of Radiation Oncology, University Hospital Heidelberg
and the German Cancer Research Center. e primary endpoint was
local-control depending on dierent resection margins. Other endpoints
were overall survival (OS), progression-free survival (PFS) and treat-
ment-related toxicity (CTCAE 4.03).
Results: Of 162 patients with OCSCC 77 patients (47.5%) had involved
(<1mm) margins, 22 patients (13.6%) close (1-5mm) margins, and 63
patients (38.9%) clear (>5mm) margins. In multivariate analysis surgical
margin < 5mm was a signicant predictor for worse local control (HR
2.6, 95% CI 1.2, 6.1), but not for OS (HR 1.2, CI 0.7, 1.9) or PFS (HR 1.2,
0.7, 2.0).
Conclusions: Especially patients with OCSCC and close margins
(1-5mm) are associated with poor local control rates and early recurrence
and benet from adjuvant radiotherapy. Further prospective studies are
needed to analyze, if a more narrow margin window could be achieved to
better determine appropriate indication of adjuvant radiation treatment.
Disclosure Statement: e authors declare no conict of interest.
573
Quality of teaching radiation oncology in times of
COVID-19 – an analysis of challenges and opportunities
Michael Oertel1; Jan C Becker2; Hans Theodor Eich1
1Klinik für Strahlentherapie - Radioonkologie, Universitätsklinikum Münster,
Münster, Deutschland
2Institut für Ausbildung und Studienangelegenheiten, WWU Münster, Münster,
Deutschland
Background: e COVID-pandemic has challenged medical education
on multiple levels. Radiation Oncology (RO) is a pivotal clinical disci-
pline for the understanding of modern oncology concepts [1]. e follow-
ing analysis aims at providing an overview of students’ evaluation of RO
teaching in the pre- and pandemic situation.
Methods: RO curriculum at our faculty is organized longitudinally span-
ning all clinical semesters which are analyzed here. Students’ evaluation is
mandatory and done on a 101-item Likert scale (0-100; with 0 being the
best grade). Starting from summer semester 2020 onward, lectures were
digitalized and digital implementation was rated on a 11-item Likert scale
(-5-+5; with -5 being the best grade). Evaluation results and participant
numbers between winter semester 2018/2019 and summer semester 2021
were assessed, the rst three semesters being classied as “pre-pandemic”
and the later three as “pandemic.
Result: Lectures were rated with a median 18.5-21.5 for the 2nd-6th clinical
semester. Comparison between pre-pandemic and pandemic semesters
revealed a deterioration of 1-3 points. Median participants numbers were
63.5-89 with an increase of 12-20 in the pandemic semesters except for
the 6th clinical semester. e percentage of students attending 75 % of RO
lectures in one semester increased considerably (median: 41.4 % vs. 75.3
%). Digital implementation was rated with a median score of -2 to 0.
Discussion: Dierences between pre-pandemic and pandemic evalua-
tions are consistent but small and are unlikely a sign of students’ discon-
tent. Digital formats could augment the numbers of participants as well as
the percentage of presence. Digital implementation was evaluated to be
average to good.
Conclusion: Digital transfer of RO is feasible and good evaluation results
are maintained. Additional concepts with a web-based learning platform
and videocasts are currently being developed.
Indication of source:
1. Oertel M et al (2020) https://doi.org/10.1007/s00066-020-01623-x
Disclosure Statement: e authors declare no conict of interest.
578
Personalized ablative treatment of lymphatic oligometastases
in the abdomen and pelvis: The SMART way
Sebastian Regnery; Carolin Buchele; Lars Piskorski; Fabian Weykamp;
Thomas Held; Tanja Eichkorn; Philipp Hoegen; Carolin Rippke;
C.Katharina Renkamp; Sebastian Klüter; Jonas Ristau; Laila König;
Sebastian Adeberg; Jürgen Peter Debus; Juliane Hörner-Rieber
RadioOnkologie und Strahlentherapie, Universitätsklinikum Heidelberg,
Heidelberg, Deutschland
Background: Oligometastatic disease requires local ablation of all malig-
nant lesions [1]. Oligometastatic spread into abdominopelvic lymph
nodes is a common scenario, particularly in prostate cancer, where pro-
spective evidence supports the benecial use of stereotactic body radio-
therapy (SBRT) [1, 2]. However, SBRT in this region can be challenging
due to the presence of sensitive organs-at-risk (OAR) and frequent prior
irradiations. Stereotactic magnetic resonance (MR)-guided online adap-
tive RT (SMART) is an innovative, personalized approach to SBRT.
Methods: 26 patients received SMART to a total of 31 oligoprogressive
lymph nodes in the abdomen and pelvis from April 2020 – April 2021
inside prospective databases. SMART was delivered on a 0.35 Tesla
MR-linac (MRIdian®, ViewRay Inc.) with calculation of the initial treat-
ment plan on the anatomy of the day (= predicted plan) and possible con-
secutive plan adaptation.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts224
Result: Most patients had prostate cancer (69 %) and most had under-
gone prior irradiations of the abdomen or pelvis (63 %). Aer a median
follow-up of 6.7 months, only one local recurrence and no case of grade ≥
3 toxicity was observed (grade 1/2 toxicity: 39 %). Comparison of 140 pre-
dicted and adapted plans revealed that daily plan adaptation signicantly
reduced inadequate planning target volume (PTV) coverage (predicted:
94%, adapted: 25%) as well as overdoses inside OAR (predicted: 19%,
adapted: 1%) and the PTV (predicted: 15%, adapted: 1%) (all p < 0.001).
Discussion: SMART allows personalized ablative irradiation with prom-
ising clinical and dosimetry results. Particularly, sensitive OAR can be
eectively protected while pursuing high PTV coverage even in challeng-
ing cases, such as re-irradiations.
Conclusion: SMART enables individualized application of ablative doses
and thus safe and eective treatment despite challenging anatomy and/or
prior irradiations.
Indication of source:
[1] Palma DA, et al. (2020). doi:10.1200/jco.20.00818
[2] Ost P, et al. (2018). doi:10.1200/jco.2017.75.4853
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
713
Monocentric comparison of denitive radio(chemo)therapy
[R(C)T] for esophageal cancer in younger (<70 years) versus
older (≥70 years) patients (pat)
Katja Döring; Sonia Ziegler; Jacqueline Possiel; Manuel Guhlich;
MarkusAnton Schirmer; Stefan Rieken; Leif Hendrik Dröge; Martin Leu
Universitätsmedizin Göttingen, Klinik für Strahlentherapie und Radioonkologie,
Göttingen, Deutschland
Background: Denitive radio(chemo)therapy [R(C)T] plays a key role in
the treatment of locally advanced inoperable esophageal cancer (LAIEC).
To date, hardly any prospective studies have been established investigat-
ing the therapy of older pat. (≥70 years), so that this retrospective study
compared therapy outcomes, toxicity and compliance between these two
pat. groups.
Methods: 151 pat. ≥18 years without distant metastasis who received
denitive R(C)T for LAIEC at our hospital between 06/1997 and 01/2021
were evaluated. Pat. and tumor characteristics, comorbidities as well as
acute and late toxicities were analyzed. e dierences between the two
groups were compared using Chi² and Mann-Whitney-U test. e pri-
mary endpoints were 5-year overall (OS) and progression-free survival
(PFS), local (LC) and distant (DC) control. Survival analysis was per-
formed by Kaplan-Meier estimator and compared using log-rank test.
Result: 72 pat. were ≥ 70 years and 79 pat. <70 years. Median follow-up
was 12.0 months (2.0-153.0). A median of 60.0 Gy (50.0 Gy - 68.4 Gy) was
applied. Patients received intensity-modulated (n=44) or 3D-conventional
radiotherapy (n=107). Brachytherapy was applied in 47 pat. 126 pat.
received concomitant chemotherapy (CTX). Pat. ≥70 years received as
many CTX treatments as younger pat. Older pat. had more comorbidities
(p<0.01). OS (22.8% vs 16.9%, p=0.31) and PFS (15.7% vs 12.9%, p=0.52)
did not signicantly dier between pat. ≥ 70 years and pat. <70 yrs. LC
(41.8% vs 53.9%, p=0.71) and DC (86.2% vs 90.0%, p=0.32) were similar
between the two groups. Acute and late toxicities did not dier signi-
cantly between the two groups.
Discussion: is retrospective study shows comparable outcome and
toxicity between younger and older pat. treated with RCT for LAIEC.
However, therapy should be strictly indicated by experienced radia-
tion oncologists with respect to comorbidities that are usually present.
Conclusion: Denitive R(C)T is a good treatment option for LAIEC, pro-
viding overall comparable LC and DC between older and younger pat.
with acceptable toxicity.
Disclosure Statement: e authors declare no conict of interest.
747
Symptom relief and oncological outcome in patients
receiving emergency radiation therapy for superior vena cava
syndrome: a single center retrospective analysis of 21 years’
practice
Teresa Esther Maag1; Leif Hendrik Dröge1; Martin Leu1; Sandra Donath1;
Felix-Nikolai Oschinka Jegor Habermann1; Markus Anton Schirmer1;
Laura Anna Fischer1; David Alexander Ziegler1; Rami El Shae1;
Stefan Rieken1; Manuel Guhlich1
1Universitätsmedizin Göttingen, Klinik und Poliklinik für Strahlentherapie und
Radioonkologie, Göttingen, Deutschland
Background: Superior vena cava syndrome (SVCS) is a group of symp-
toms caused by obstruction of the superior vena cava. Leading symptoms
are shortness of breath and swelling of neck and face. SVCS can lead to
several life-threatening consequences, e.g. brain edema. Mainly caused by
malignant tumor growth, progressed SVCS oen presents as a medical
emergency. erapies include glucocorticoids, chemotherapy, endovascu-
lar stenting and urgent radiotherapy (RT).
Methods: To evaluate treatment outcomes, we examined patients receiving
RT for SVCS in the Department of Radiation erapy and Radiooncology,
University Medical Center in Göttingen, in the years 2000 – 2020. Local
ethics committee approval was obtained, data was retrieved from the
patients’ medical records. Primary endpoint was symptom relief; second-
ary endpoints were oncological outcome and treatment-related toxicity.
Result: 132 patients were screened, 83 patients were eligible for analysis.
Main diagnosis was bronchial carcinoma (65 patients; 78,3%). 25 patients
(30,1%) did not nish RT; 16 patients (19,3%) died during therapy, three
of which received only one or two RT fractions.
Clinical symptom relief was achieved In 43 patients (65,2%), 23 patients
(34,8%) did not benet clinically. In 17 patients, no data was available.
40 patients (48,2%) showed any RT related side eects, 25 patients (30,1%)
at least toxicity grade 2 as scored by Common Toxicity Criteria, V5.0.
Primary toxicity was dysphagia (total 27 patients, 32,5%, ≥ grade 2: eight
patients, 9,6%).
Patients’ mean overall survival was 104,7 days (range: 2-929). 18 Patients
were lost to follow up. ree patients were still alive at last follow-up
(08/2021).
Discussion: Our data show a clinical symptom relief for 65% of patients
suering from SVCS. Outcomes may be biased due to individual physi-
cians’ assessment, causing primary tumor and concomitant therapies.
Conclusion: RT for SVCS is a feasible and oen benecial emergency
procedure with acceptable acute side eects. Even though it oen occurs
in advanced cancer, long-term survival can be achieved.
Disclosure Statement: e authors declare no conict of interest.
757
Symptom relief and oncological outcome in patients receiving
emergency radiation therapy for acute tumor associated
hemoglobin relevant bleedings: a single center retrospective
analysis of 21 years´ practice
Teresa Esther Maag1; Andrea Hille1; Rami El Shae1; Sandra Donath1;
Stephanie Bendrich1; Friedemann Nauck2; Martin Leu1;
Leif Hendrik Dröge1; Laura Anna Fischer2; Markus Anton Schirmer1;
Stefan Rieken1; Manuel Guhlich1
1Universitätsmedizin Göttingen, Klinik und Poliklinik für Strahlentherapie und
Radioonkologie, Göttingen, Deutschland
2Universitätsmedizin Göttingen, Klinik für Palliativmedizin, Göttingen,
Deutschland
Background: Acute tumor associated hemoglobin relevant bleeding
(ATAHRB) is a rather frequent and feared complication in oncology.
Depending on the localisation of the haemorrhage, established therapies
include compression, sclerotherapy, radiological intervention and urgent
radiotherapy (RT).
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 225
Methods: To evaluate treatment outcomes in emergency RT for ATAHRB,
we examined patients treated in the Department of Radiation erapy
and Radiooncology, University Medical Center in Göttingen, Germany,
in the years 2000 – 2020. Local ethics committee approval was obtained,
data was retrieved from the patients’ medical records. Primary Endpoint
was bleeding stop; secondary endpoints were oncological outcome and
treatment-related toxicity.
Result: 101 patients were screened. A total of 84 patients were eligible
for analysis. 33 patients (39,3%) were treated for gynaecological carci-
noma, 19 patients (22,6%) for urological carcinoma, eight patients (9,5%)
for gastrointestinal carcinoma, seven patients (8,3%) for lung cancer; 17
patients (20,2%) for other tumors.
In 75 patients (89,3%), a bleeding stop was reported clinically. Eight
patients (9,5%) did not benet, in one patient (1,2%), no data was avail-
able. 14 patients (16,7%) did not nish the treatment, ve patients (6%)
died during therapy.
41 patients (48,8%) showed any radiation related side eects, 18 patients
(21,4%) at least toxicity grade 2 as scored by Common Toxicity Criteria,
V5.0. Most patients (n=32, 38,1%) suered from gastrointestinal and/or
genitourinary side eects, 8 patients (9,5%) at least grade 2.
Mean overall survival (OS) was 344,2 days (range: 3-5455). 31 patients
were lost to follow up. One patient was still alive at last follow-up (08/2021).
Discussion: Consistent with previously published data, our results show
a highly eective therapy for ATAHRB. Remarkably, mean OS in this pri-
marily palliative patient cohort was 344 days.
Conclusion: RT for ATAHRB proved to be a safe and very eective emer-
gency procedure with acceptable acute side eects.
Disclosure Statement: e authors declare no conict of interest.
783
Irradiation of the source cells impacts the eects of secreted
exosomes in target cells
Mahtab Lashgari1; Bettina Priesch-Grzeszkowiak1; Anja Grillenberger1;
Pascaline Kouam-Daniel1; Jan P. Boström2; Irenäus A. Adamietz1; Helmut
Bühler1
1Klinik für Strahlentherapie und Radio-Onkologie, Universitätsklinikum Marien
Hospital, Herne, Deutschland
2Gamma Knife Zentrum, Knappschaftskrankenhaus Bochum, Bochum,
Deutschland
Background: We investigated whether exosomes from glioblastoma cells
aect malignancy when taken up by cells of the same lineage and whether
dierences exist when the secreting cells were previously irradiated.
Methods: e malignancy parameters motility, invasiveness, prolifera-
tion, and clonogenic survival were examined by videography, 3d matrix
degradation, colorimetric viability assay, and colony formation.
Result: Both exosome fractions signicantly aected the parameters
studied with signicant dierences between the two fractions. Overall, it
appeared that exosomes from unirradiated cells signicantly increased the
malignancy of target cells, while exosomes from irradiated cells tended to
reduce it.
Discussion: Malignant cells appear to communicate materially via exo-
somes and pass on the information "irradiated" in this way.
Conclusion: It is possible that this is a mechanism that contributes to
bystander and abscopal eects.
Disclosure Statement: e authors declare no conict of interest.
Rehabilitation and long-term burden in social medicine (survivor)
Best-of-Abstract-Vortrag
92
Treatment decision regret in long-term prostate cancer
survivors after radical prostatectomy: a longitudinal study
Valentin H. Meissner1; Barbara W. Simson1; Andreas Dinkel2; Stefan
Schiele1; Donna Ankerst3; Jürgen Gschwend1; Kathleen Herkommer1
1Technische Universität München, Klinik und Poliklinik für Urologie,
Universitätsklinikum rechts der Isar, München, Deutschland
2Technische Universität München, Klinik und Poliklinik für Psychosomatische
Medizin und Psychotherapie, Universitätsklinikum rechts der Isar, München,
Deutschland
3Technische Universität München, Lehrstuhl für Mathematische Modelle
biologischer Systeme, Fakultät für Mathematik, Garching, Deutschland
Background: Patients diagnosed with localized prostate cancer (PC) have
to choose between several treatment options. Treatment complications
and poor oncologic outcomes can lead patients to regret their initial treat-
ment choice.
Methods: 1,003 survivors from the multicenter German Familial PC data-
base submitted questionnaires on treatment decision regret in 2007 (T1)
on average 7 years aer radical prostatectomy and then again 13 years
later in 2020 (T2). Patients completed standardized patient-reported
outcome measures on decision-making, quality of life, and psychosocial
factors. Hierarchical multivariable logistic regression was used to assess
predictors of longitudinal decision regret.
Result: Decision regret increased signicantly over time (9.0% aer 6.9
years in 2007 and 12.1% aer 19.9 years in 2020; p=0.009). Patients with
stable decision regret at both time points reported signicantly more
oen a passive decision-making role compared to patients with stable no
decision regret (27.8% vs. 10.6%; p=0.005). Patients with stable no deci-
sion regret had higher scores in quality of life compared to patients with
stable and increasing decision regret, respectively (0.69 vs. 0.65 and 0.62,
respectively; p=0.013). Organ-conned disease (OR 1.82, 95% CI 1.03-
3.21), decision regret in 2007 (OR: 6.40, 95% CI 3.56-11.51), and a higher
depression score (OR 1.42 95% CI 1.07-1.89) were associated with deci-
sion regret in 2020. Shared decision-making (OR: 0.55 95% CI 0.32-0.92)
was associated with less decision regret.
Discussion: A profound understanding of determinants of decision regret
may optimize the initial treatment decision making process leading to
lower decision regret and quality of life improvements in PC survivors.
Conclusion: Findings of the present study underline the perseverance
of decision regret in long-term PC survivors and the denitive need for
involving patients in the decision-making process to mitigate regret over
the long term.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts226
Poster
55
Health and Nutritional Status after radical prostatectomy
Marc Heydenreich1; Alexander Stäuber2; Dirk-Henrik Zermann1
1Vogtland-Klinik Bad Elster, Bad Elster, Deutschland
2Chemnitz University of Technology, Professorship of Sports Medicine / Sports
Biology, Chemnitz, Deutschland
Background: e Bioelectrical Impedance Analysis (BIA) enables an
assessment of the body compartments and the phase angle is used to
assess the course of the disease (1, 2). e aim of the study was, what
inuence does the stress associated with diagnostics and therapy have on
the phase angle aer radical prostatectomy.
Methods: A total of 103 patients aer radical prostatectomy were exam-
ined using BIA.
Result: 40–55-year-old patients (n=8): BMI= 28.2; phase angle 5.6 (0.3);
reference value 6.5 (0.2)
56-70-year-old patients (n=62): BMI= 27.9; phase angle 5.2 (0.6); refer-
ence value 6.0 (0.2)
71-85--year-old patients (n=33): BMI= 26.4; phase angle 4.7 (0.8); refer-
ence value 5.3 (0.2)
Discussion: e results show that a lower phase angle is measured with
increasing age. As a result, older prostate cancer patients have a poorer
nutritional or health status.
In comparison to the age-specic normal value, the phase angle in patients
aer radical prostatectomy is signicantly lower (Bosy-Westphal 2006).
Conclusion: According to current scientic knowledge, the phase angle
allows conclusions about nutritional-, hydration-, functional status and the
morbidity and mortality risk of the patient (Stobäus 2010). Consequently,
the tasks of rehabilitation and aercare is restoring an adequate training
and nutritional status aer completing primary cancer therapy. In addi-
tion to targeted physiotherapeutic and sports science treatments, this also
requires nutritional medical interventions.
Indication of source:
1. Bosy‐Westphal A, Danielzik S, Dörhöfer RP, Later W, Wiese S, Müller MJ.
Phase angle from bioelectrical impedance analysis: population reference values
by age, sex, and body mass index. Journal of Parenteral and Enteral Nutrition.
2006;30(4):309-16.
2. Stobäus N, Norman K, Pirlich M. Phasenwinkel und Bioelektrische Impedanz-
vektoranalyse–Klinische Anwendbarkeit der Impedanzparameter. Aktuelle
Ernährungsmedizin. 2010;35(03):124-30.
Disclosure Statement: e authors declare no conict of interest.
Poster
Rehabilitation and long-term burden in social
medicine (survivor)
230
Degree of urinary incontinence after neobladder surgery -
variation in last ten years
Marc Heydenreich; Dirk-Henrik Zermann
Vogtland-Klinik Bad Elster, Bad Elster, Deutschland
Background: Overcoming urinary incontinence aer cystectomy and
forming a neobladder is a particular challenge. e aim of this study was
to evaluate the development of the continence situation aer creation of a
neobladder in the period from 2010 to 2020.
Methods: 621 neobladder patients performed a 24-hour Pad Test at the
beginning of a 3-week-rehabilitation. For the statistical evaluation, an
SQL query of the data from 2010-2020 was carried out and evaluated.
Result:
year 2010 (n=68): urine loos/ 24h= 587.1g
year 2011 (n=57): urine loos/ 24h= 617.0g;
year 2012 (n=51): urine loos/ 24h= 395.3g;
year 2013 (n=63): urine loos/ 24h= 517.9g;
year 2014 (n=53): urine loos/ 24h= 573.2g;
year 2015 (n=58): urine loos/ 24h= 536.5g;
year 2016 (n=61): urine loos/ 24h= 609.4g;
year 2017 (n=62): urine loos/ 24h= 567.3g;
year 2018 (n=66): urine loos/ 24h= 538.1g;
year 2019 (n=46): urine loos/ 24h= 661.6g;
year 2020 (n=36): urine loos/ 24h= 434.5g;
Discussion: e postoperative 24-hour urine loss is 552.8 g/ 24h on aver-
age (varying between min. 2 g and max. 3170 g).
Conclusion: e results show that the early postoperative amounts of
urine lost aer neobladder are subject to variation in the period from 2010
to 2020. A trend towards reduction over the last ten years, as in the case
of post-radical prostatectomy, cannot be demonstrated [1]. is is most
likely due to the complex anatomical and physiological changes that result
from the neobladder. is underlines the importance of individual reha-
bilitation treatment and enables timely progress through a combination of
dierent continence and coordination techniques [2].
Indication of source:
1. Heydenreich M, Zermann DH, Historische Entwicklung der Harnverlustmen-
gen nach radikaler Prostatektomie von 2010–2019, Der Urologe; 2020.
2. Heydenreich M, Zermann DH, Harninkontinenz nach Anlage einer
Neoblase– Ezienz eines sensomotorischen Trainings, Der Urologe; 2020.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 227
Poster
Rehabilitation and long-term burden in social
medicine (survivor)
419
Ecacy of a memory and psychomotor intervention in
cancer-related cognitive impairment: design of a randomized
controlled trial
Joschua Mirko Reis1; Anna Ballweg1; Mia Wallis1; Antonia Rabe2;
Ralf C. Bargou3; Elisabeth Jentschke2
1Faculty of Medicine , Julius-Maximilians University of Würzburg, Medical
Student, Würzburg, Deutschland
2Comprehensive Cancer Center Mainfranken, University Hospital Würzburg,
Psychoonkology, Würzburg, Deutschland
3Comprehensive Cancer Center Mainfranken, University Hospital Würzburg,
Würzburg, Deutschland
Background: Cancer patients oen suer from impairments in their
cognitive functionality. An intervention consisting of memory and psy-
chomotor training (MPMT) improved cognition of geriatric patients
(Oswald et al., 2006). A comparable intervention has not been evaluated
in patients with cancer-related cognitive impairment (CRCI) yet. e aim
of the study is to investigate eects of MPMT intervention on cognition
in patients with CRCI.
Methods: Adult patients with dierent types of cancer and treatment
will be recruited at the University Hospital Würzburg. Recruitment
begins in autumn 2021. Study participants will be randomly assigned to
MPMT intervention or waiting group including standard treatment in a
1:1 ratio. MPMT is an 8-week online training made for groups of 8 (1h/
week). Participants complete assessments at baseline, post-intervention,
and 6 months post-intervention. Assessments examine cognitive func-
tion (Test battery for the assessment of attentional functioning (Alertness,
Go-/Nogo, working memory), Verbal Learning and Memory Test, Trail
Making Test, FACT-Cog), physical performance (6-minute-walk test),
quality of life (EORTC-QLQ-30), experienced attention decits (FEDA)
and potential confounders such as anxiety (GAD-7), depression (PHQ-9),
distress (Distress ermometer), comorbidities (e. g. cancer-related
fatigue (EORTC-QLQ-FA12)). e primary outcome is the alertness of
participants in the intervention group compared to those in the control
group. Necessary sample size is 152 subjects (power 80%; p-level <0.05;
R2 = 0.5; drop-out rate of 20%, PASS 2020). Dierences between groups
are determined by using an analysis of covariance.
Discussion: is study is the rst randomized controlled trial that exam-
ines changes in cognitive functions of a MPMT online group intervention
in patients with CRCI. A limitation is that blinding of patients is not possi-
ble due to usual care in the control group and could lead to placebo eects
in the intervention group.
Disclosure Statement: e authors declare no conict of interest.
Poster
Rehabilitation and long-term burden in social
medicine (survivor)
455
Development and evaluation of the website Onko-Vital
for the oncological rehab-aftercare
Heike Kähnert1; Birgit Leibbrand2
1Institut für Rehabilitationsforschung, Norderney, Bad Salzuen, Bad Salzuen,
Deutschland
2Salzetalklinik, Bad Salzuen, Deutschland
Background: In this study we present the development and initial review
of Onko-Vital: an online rehab aercare program. A participatory devel-
opment process is a central aspect of this project to align the Onko-Vital
website with the needs of oncological patients.
Methods: For the development of the website, oncological patients were
asked about the design and content of online rehab aercare programs via
group interviews (n = 4) and questionnaires (n = 130). Both the Onko-
Vital prototype and the associated Onko-Vital training were subjected to
an initial review with oncological patients (n = 50).
Results: According to the participants, an online rehab aercare pro-
gram should provide information, tutorials, and tips on therapy-related
side eects (approval: 83%), nutrition (90%), physical activity (80%), and
mental health (66%). In addition, a forum (42%) and the possibility of
recording their own aercare goals (54%) should be part of the program.
During rehab, training session on website use should be oered (78%).
In addition, the interviews provide insight into the users perception on
usability and clarity of the website. During the pilot phase, the participants
received the Onko-Vital training in the second rehab week and were able
to use the website on a smartphone or tablet from the third rehab week.
94% of the participants rated the training as (very) good and 96% as prac-
tical. Furthermore, 94% of the participants felt(very) good prepared on
how to use the Onko-Vital website aer the training concluded. At the end
of the rehab, the website is rated as versatile (86%), professional (86%),
and attractively designed (92%). e handling of Onko-Vital is easy to
understand (78%), aiding the user’s orientation and ability to search for
specic information (72%). 94% of the participants want to use the web-
site at home.
Conclusions: e development of Onko-Vital was successfully completed
through a participatory process. Onko-Vital is accepted by patients and
rated overwhelmingly positive. An RCT-study is currently being carried
out to check the eectiveness of Onko-Vital.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts228
Poster
Rehabilitation and long-term burden in social
medicine (survivor)
851
Return to work, fatigue and cancer rehabilitation after
curative radiotherapy and radiochemotherapy for pelvic
gynecologic cancer
Eva Meixner1,2,3; Ilse Weis4; Daniela Roob4; Elisabetta Sandrini1,2,3;
Line Hoeltgen1,2,3; Tanja Eichkorn1,2,3; Philipp Hoegen1,2,3; Laila König1,2,3;
Nathalie Arians1,2,3; Markus Wallwiener5; Jürgen Peter Debus1,2,3;
Juliane Hörner-Rieber1,2,3
1Abteilung für RadioOnkologie und Strahlentherapie, Universitätsklinikum
Heidelberg, Heidelberg, Deutschland
2Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Deutschland
3National Center for Tumor diseases (NCT), Heidelberg, Deutschland
4Social Service Counselling, Heidelberg University Hospital, Heidelberg,
Deutschland
5Department of Gynecology and Obstetrics, Heidelberg University Hospital,
Heidelberg, Deutschland
Background: Pain, fatigue and depression are a common cluster of symp-
toms among cancer patients that impair quality of life and daily activities.
We aim to evaluate the burden of cancer rehabilitation, return to work
(RTW) and a more in-depth understanding of the impacts of treatment
for post-therapy recovery.
Methods: Tumor and treatment characteristics, lifestyle and house-
hold data, the use of in-house social services, post-treatment inpatient
rehabilitation and RTW were assessed for 424 women, diagnosed with cer-
vical, uterine, vaginal and vulvar cancer, receiving curative radio(chemo)
therapy.
Result: RTW rates for progression-free women aer RT at 3 and 6 months
were 32.3% and 51.0%, and increased at 12 and 18 months to 58.1% and
63.2%, respectively. Progressive disease, the presence of fatigue or pain,
salaried employment, depression and a body weight outside normal
ranges were signicantly associated with lower RTW rates. Patients with
higher FIGO stages and intensied treatment signicantly suered from
more acute pain and fatigue. e Charlson Comorbidity Index reliably
predicted patients associated with signicantly higher rates of fatigue.
Aside from the presence of children, no other household/lifestyle factor
was correlated to increased fatigue rates. Women aged ≤45 years had a sig-
nicantly higher risk of developing depression requiring treatment during
follow-up. Post-treatment inpatient cancer rehabilitation, including exer-
cise and nutrition counseling, signicantly relieved fatigue symptoms.
Discussion: Social support services and post-treatment inpatient cancer
rehabilitation programs were helpful in keeping patients connected to
their professional lives. Mental issues and the development of depression
during follow-up remains an issue particularly for younger patients.
Conclusion: e burdens for recovery from cancer therapy remain
multi-factorial. Special focus needs to be placed on identifying high-risk
groups experiencing fatigue or pain. Specialized post-treatment inpatient
cancer rehabilitation can improve RTW rates.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
Poster
Rehabilitation and long-term burden in social
medicine (survivor)
997
Quality of life in long-term survivors of pediatric cancer in
comparison with the general population and associations
with health behavior, health risk factors, and physical illness
Mareike Ernst1; Andreas Hinz2; Elmar Brähler1; Jörg Faber3; Philipp S. Wild4;
Hiltrud Merzenich5; Manfred E. Beutel1
1Klinik und Poliklinik für Psychosomatische Medizin und Psychotherapie,
Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz,
Deutschland
2Abteilung für Medizinische Psychologie und Medizinische Soziologie,
Universitätsklinikum Leipzig, Leipzig, Deutschland
3Pädiatrische Hämatologie/Onkologie/Hämostaseologie, Universitätsmedizin
der Johannes Gutenberg-Universität Mainz, Zentrum für Kinder- und
Jugendmedizin, Mainz, Deutschland
4Präventive Kardiologie und Medizinische Prävention, Universitätsmedizin
der Johannes Gutenberg-Universität Mainz, Zentrum für Kardiologie, Mainz,
Deutschland
5Institut für Medizinische Biometrie, Epidemiologie und Informatik,
Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz,
Deutschland
Background: We aimed to compare the quality of life (QOL) reported by
childhood cancer survivors (CCS) drawn from a cohort of the German
Childhood Cancer Registry with a representative population sample and,
within CCS, to test associations between QOL and health behavior, health
risk factors, and physical illness.
Methods: CCS (N = 633, age at diagnosis M = 6.34 (SD = 4.38), age at
medical assessment M = 34.92 (SD = 5.70)) and a general population sam-
ple (age-aligned; N = 975) lled out the EORTC QLQ-C30. Comparisons
were performed using General linear models (GLMs) (xed eects: gen-
der, group (CCS vs. population); covariates: age, education level). CCS
underwent an extensive medical assessment (mean time from diagnosis
to assessment was 28.07 (SD = 3.21) years) including objective diagno-
sis of health risk factors and physical illnesses (e.g., diabetes and cardio-
vascular disease). Within CCS, we tested associations between QOL and
sociodemographic characteristics, health behavior, health risk factors, and
physical illness.
Result: CCS reported both worse functional QOL and higher symptom
burden than the population. Female CCS reported particularly low QOL
and high symptom burden. Among CCS, better total QOL was related to
younger age, higher level of education, being married, and engaging in
active sports. Both health risk factors and manifest physical illnesses were
associated with lower total QOL.
Discussion: In all domains, long-term CCS reported worse QOL than the
comparison sample.
Conclusion: e negative associations with risk factors and physical
illnesses indicate an urgent need for long-term surveillance and health
promotion.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 229
Sarcoma
Best-of-Abstract-Vortrag
486
A post hoc analysis of the EPAZ trial: the role of geriatric
variables in elderly soft tissue sarcoma (STS) patients on
toxicity and outcome
Rainer Hamacher1,2; Xiaofei Liu3; Markus K. Schuler4; Leopold Hentschel5;
Patrick Schöski6; Hans-Georg Kopp7; Sebastian Bauer1,2; Bernd Kasper8;
Lars Lindner9; Jens Chemnitz10,11; Martina Crysandt12; Alexander Stein13;
Björn Steen14; Stephan Richter5; Gerlinde Egerer15; Philipp Ivanyi16;
Annegret Kunitz17,18; Viktor Grünwald2,19,20
1Department of Medical Oncology, Sarcoma Center, West German Cancer
Center, University Hospital Essen, Essen, Deutschland
2German Cancer Consortium (DKTK), Partner site University Hospital Essen
3Institute for Biostatistics, Medical School Hannover, Hannover, Deutschland
4MVZ Onkologischer Schwerpunkt am OHH, Berlin, Deutschland
5University Hospital Carl Gustav Carus, University Cancer Center/Medical
Department I, Dresden, Deutschland
6Department of General Medical Oncology, University Hospitals Leuven, Leuven
Cancer Institute, KU Leuven, Löwen, Belgien
7Robert Bosch Centrum für Tumorerkrankungen Stuttgart, Stuttgart,
Deutschland
8Sarcoma Unit, Mannheim University Medical Center, Mannheim, Deutschland
9Department of Medicine III, University Hospital, Ludwig Maximilian University
Munich, München, Deutschland
10Community Hospital Middle Rine, Koblenz, Deutschland
11Department of Hematology, Oncology, Clinical Infectious Diseases, Clinical
Immunology, Hemostaseology and Medical Intensive Care, University Hospital
Cologne, Köln, Deutschland
12University Hospital RWTH Aachen, Aachen, Deutschland
13University Hospital Hamburg-Eppendorf, Hamburg, Deutschland
14University Hospital Frankfurt, Frankfurt am Main, Deutschland
15University Hospital Heidelberg, Heidelberg, Deutschland
16Clinic for Hematology, Hemostasis, Oncology and Stem Cell Transplantation, ,
Medical School Hannover, Hannover, Deutschland
17Vivantes Clinic Berlin-Spandau, Berlin, Deutschland
18Department of Hematology, Oncology and Tumor Immunology, University
Hospital Charite, Berlin, Deutschland
19Interdisciplinary Genitourinary Oncology at the West German Cancer Center,
Clinic for Internal Medicine (Tumor Research) and Clinic for Urology, University
Hospital Essen, Essen, Deutschland
20Clinic for Hematology, Hemostasis, Oncology and Stem Cell Transplantation,
Medical School Hannover, Hannover, Deutschland
Background: e EPAZ study (NCT01861951) recently showed that
pazopanib was non-inferior to doxorubicin in patients ≥ 60 years treated
in rst line for advanced STS [1].
Methods: Patients ≥ 60 years with advanced STS were randomized for
treatment with either pazopanib or doxorubicin. Geriatric assessment [G8
screening tool, Charlson Comorbidity Index (CCI), instrumental activ-
ities of daily living (IADL) and social situation] were assessed at base-
line. Age > 75 years, liposarcoma, ECOG = 2, G8 ≤ 14, IADL ≥ 1 and
CCI ≥ 2 were tested for their impact on progression-free survival (PFS),
overall survival (OS), CTCAE grade 3/4 adverse events (AEs) or serious
AEs (SAEs), using Kaplan-Meier method and Cox proportional hazards
model. Treatment was always included as a covariate in the Cox model.
Result: Univariate analysis showed an increased risk of grade 3/4 AEs and
SAEs for ECOG = 2, G8 score ≤ 14 and IADL ≥ 1, independent of treat-
ment. Multivariate analysis showed for pazopanib a signicant reduced
risk for grade 3/4 AEs (HR 0.53; p = 0.033) and G8 ≤ 14 an increased
risk for SAEs (HR 2.67; p = 0.011). Regarding outcome, on multivari-
ate analysis, G8 ≤ 14 was a negative prognostic factor for PFS (HR 1.82;
p = 0.009) and IADL ≥1 for OS (HR 2.02; p = 0.007). ECOG = 2 was
the strongest negative predictor for PFS (HR 4.39; p = 0.001) and OS
(HR 3.74; p = 0.004). Neither age nor CCI showed any impact on PFS, OS,
grade 3/4 AEs or SAEs.
Discussion: is post hoc analysis demonstrated that age is not a denom-
inator for outcome or toxicity in elderly STS patients. Instead, functional
assessment is of prognostic and predictive value. Moreover, pazopanib has
a reduced risk for grade 3/4 AEs compared to doxorubicin.
Conclusion: Geriatric assessment should be used to counsel patients and
tailor therapy to individual needs.
Indication of source:
1 Grünwald V, Karch A, Schuler M, Schöski P, Kopp HG, Bauer S, et al. Rando-
mized Comparison of Pazopanib and Doxorubicin as First-Line Treatment in
Patients With Metastatic So Tissue Sarcoma Age 60 Years or Older: Results of
a German Intergroup Study. J Clin Oncol. 2020;38(30):3555-64.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
Poster
177
High-grade osteosarcoma of bone of elderly patients (65+
years): Results of the cancer registry Baden-Württemberg
Miriam Wilhelm1; Irina Surovtsova2; Marlies Günther-Gunkel3; Philipp
Morakis4
1Klinische Landesregisterstelle des Krebsregisters Baden-Württemberg,
Geschäftsstelle Qualitätskonferenzen, Stuttgart, Deutschland
2Klinische Landesregisterstelle des Krebsregisters Baden-Württemberg,
Stabsstelle Statistik, Stuttgart, Deutschland
3Klinische Landesregisterstelle des Krebsregisters Baden-Württemberg,
Datenmonitoring, Stuttgart, Deutschland
4Klinische Landesregisterstelle des Krebsregisters Baden-Württemberg, Leitung
Geschäftsstelle Qualitätskonferenzen, Stuttgart, Deutschland
Purpose: In these results we report characteristic at diagnosis as well as
treatment of elderly osteosarcoma patients in Baden-Württemberg.
Methods: To present patient´s characteristics (age, gender, histology, site,
primary metastases, pre-existing cancer disease), treatment (systemic-
and radiotherapy, operation) and outcome (vital status) patients (aged
65 +) with high-grade osteosarcoma (ICD-O: 9180/3, 9181/3, 9182/3,
9183/3, 9184/3, 9185/3 or 9186/3) that were reported to the cancer regis-
tration since 2012 were included in these analyses.
Preliminary Results: Data of 32 patients with high-grade osteosarcoma of
bone were registered between 2012 and 2020 (15 males, 17 females), mean
age was 73 years, 39% had primary metastases (unknown 9 patients).
Tumor site: extremity 15, trunk 12 (including 5 pelvis), craniofacial 5. 22
patients received surgery, 8 radiotherapy, 10 chemotherapy, for 11 patients
out of these it was a combination of therapies (no therapy reported 4).
Discussion: Elderly patients are oen excluded in study protocols and
data in non-obligatory registries is incomplete. e data from popula-
tion-based registries however, can provide insights on specic subgroups.
e data presented here are not in line with the results reported by Longhi
et al. (2008; Osteosarcoma in patients older than 65 years. J Clin Oncol.
26(33), 5368-5373) for site and treatment. is may be due to therapy
changes since 2008 as well as to the dierent source and structure of data
collection.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts230
Conclusion: Even though the database of cancer registries has limitations
concerning clinical data when compared to clinical studies or detailed
patient chart information, this population based data is very evaluable,
especially for rare diseases such as osteosarcoma. Due to region-wide
mandatory notication of a standardized dataset, detailed evaluations of
rare cancer diseases are possible.
Disclosure Statement: e authors declare no conict of interest.
219
A novel immune-related gene signature predicting survival in
sarcoma
Haoyu Ren1; Alexandr Bazhin1,2; Elise Pretzsch1; Sven Jacob1; Haochen Yu1;
Jiang Zhu3; Markus Albertsmeier1; Lars Lindner4; Thomas Knösel5;
Jens Werner1,2; Martin Angele1,2; Florian Bösch1,6
1Ludwig-Maximilians-University Munich, Department of General, Visceral, and
Transplant Surgery, Munich, Deutschland
2German Cancer Consortium (DKTK), Partner Site Munich, Munich, Deutschland
3West China Hospital, Sichuan University, Department of Liver Surgery and Liver
Transplantation Centre, Chengdu, China, VR
4University Hospital, LMU Munich, Department of Medicine III, SarKUM, Munich,
Deutschland
5University Hospital, LMU Munich, Institute of Pathology, Munich, Deutschland
6University Medical Center Goettingen, Department of General, Visceral and
Pediatric Surgery, Goettingen, Deutschland
Background: Sarcomas are a heterogeneous group of rare mesenchymal
tumors. e current risk stratication system is insucient to provide
precise survival prediction and treatment response. us, valid prognostic
models are needed to guide treatment.
Methods: is study analyzed the gene expression and outcome of 980 sar-
coma patients from seven public datasets. e abundance of immune cells
and the response to immunotherapy was calculated in the ImmuCellAI
database. Immune-related genes (IRG) were screened through weighted
gene co-expression network analysis (WGCNA). LASSO Cox regression
was used to establish a powerful IRG signature predicting prognosis. We
divided patients into high and low-risk groups based on the risk score of
the IRG signature and compared survival between groups. Moreover, we
developed a nomogram and a decision tree integrating the IRG risk score
and clinicopathological parameters.
Result: e identied IRG signature incorporated 14 genes and identied
high-risk patients in the training and six validation cohorts. Multivariate
survival analyzes revealed that the 14-IRG signature served as an indepen-
dent risk factor for overall and disease-free survival. Moreover, the IRG
signature acted as a potential indicator for immunotherapy. e nomo-
gram based on the IRG signature risk score outperformed presented tra-
ditional clinicopathological features in survival prediction. e decision
tree discriminated risk subgroups powerfully.
Discussion: In the developed 14-IRG signature, TRIM21 and NT5DC2
may be the novel biomarkers and therapeutic target for sarcoma. A nomo-
gram and a decision tree based on the IRG signature act as an accurate and
practical predictive tool identifying high-risk patients with low survival
rates. It also provides an opportunity to identify patients with sarcomas
eligible for immune checkpoint inhibitor therapy.
Conclusion: In summary, the proposed IRG signature is a robust bio-
marker to predict outcome and treatment response in sarcoma patients.
Disclosure Statement: e authors declare no conict of interest.
251
Prophylactic lymphaticovenous anastomoses for resection
ofsoft tissue tumors of the thigh
Johannes Maximilian Wagner; Mehran Dadras; Markus Lehnhardt;
Bjoern Behr
Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil Bochum,
Plastische Chirurgie, Bochum, Deutschland
Purpose: Patients with so tissue tumors of the extremities are at risk
to develop secondary lymphedema aer tumor resection caused by dis-
ruption of lymphatic vessels and sclerosis. Lymphaticovenous anastomo-
sis (LVA) is a minimally invasive procedure capable of creating a bypass
for restoration of lymphatic drainage in early stages of lymphedema. is
study aimed to evaluate the benecial eects of LVAs aer so tissue tumor
resection of the thigh in a prophylactic approach. Methods: In a retro-
spective case control study, we compared 8 patients who received LVAs in
combination with tumor resection for the treatment of so tissue tumors
of the thigh with a prior cohort of 20 patients who received so tissue sar-
coma resection of the thigh. All patients receiving LVA were assessed for
development of lymphedema via bilateral measurements of circumference
and assessment of lymphedema quality of life index (LyQLI). Outcome
data were obtained from the control cohort by assessment of swelling of
the aected limb, need for compression garments and the LyQLI.
Results: Only one of the eight patients who received LVAs showed moder-
ate impairment in the LyQLI at a follow-up of 12 months while 45% of the
control cohort patients complained about symptoms of secondary lymph-
edema at a median follow-up of 22 months. Furthermore, no lymphedema
could be observed in circumferential and ICG measurements in LVA
patients.
Discussion: LVAs performed in combination with tumor resection
of thigh so tissue tumors could eectively reduce the negative conse-
quences of lymph transport disruption and prevent development of sec-
ondary lymphedema.
Conclusion: Although performing LVAs in most patients with so tissue
tumors would be favorable, this procedure should be limited to patients
who are at a high-risk developing lymphedema such as large tumors
located adjacent to dominant lymph paths of the extremities.
Disclosure Statement: e authors declare no conict of interest.
292
Fusion of preoperative in situ magnetic resonance imaging
and postoperative computed tomography of the specimen
to correlate functional imaging features and pathological
characteristics of soft tissue sarcoma
Madelaine Hettler1; Julia Kitz2; Manuel Guhlich3; Ali Seif4; Jennifer Ernst5;
Lena-Christin Conradi1; Michael Ghadimi1; Philipp Ströbel2; Jens Jakob6
1Universitätsmedizin Göttingen, Klinik für Allgemein-, Viszeral- und
Kinderchirurgie, Göttingen, Deutschland
2Universitätsmedizin Göttingen, Institut für Pathologie, Göttingen, Deutschland
3Universitätsmedizin Göttingen, Klinik für Strahlentherapie und
Radioonkologie, Göttingen, Deutschland
4Universitätsmedizin Göttingen, Institut für Diagnostische und Interventionelle
Radiologie, Göttingen, Deutschland
5Universitätsmedizin Göttingen, Klinik für Unfallchirurgie, Orthopädie und
Plastische Chirurgie, Göttingen, Deutschland
6Universitätsmedizin Mannheim, Chirurgische Klinik, Mannheim, Deutschland
Background: Treatment and prognosis of so tissue sarcoma (STS) are
mainly based on histological subtype and grading. However, pretherapeu-
tic biopsies oen do not provide reliable tumor characterization due to
tumor size and intratumorale heterogeneity. By combining histopatho-
logic and functional imaging features the pretherapeutic grading might
be improved.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 231
Methods: Twelve patients with histologically conrmed STS were
included in the prospective pilot study. A preoperative diusion weighted
MRI was performed. Aer tumor resection, we collected core needle
biopsies (CNB) from several regions from the surgical specimen and le a
radiopaque marker at each biopsy site. Aerwards the markers were visu-
alized in a CT of the specimen. To evaluate the imaging features of the
exact sampling regions, fusion imaging of preoperative MRI and postop-
erative CT was performed. Grading by FNCLCC and apparent diusion
coecient (ADC) on functional MRI were determined for all specimens
and CNBs.
Result: In 7/12 cases, fusion imaging of pretreatment imaging and post-
operative CT of the resected specimen was feasible without relevant con-
tour deviations. Histological workup resulted in correct grading in 9/11
cases (81,8 %, in n=2: G1 instead of G2). Functional evaluation shows
a tendency for high-grade STS regions to have lower ADC values than
low-grade regions.
Discussion: Due to the challenging histopathological grading of STS,
there are already several attempts to develop a radiological grading.
However, these approaches currently do not provide suciently reliable
results. erefore, the supplementation of histopathological grading by
ADC is suggested to be a useful option to improve the grading of STS.
Conclusion: Our pilot study demonstrates the technical feasibility of cor-
relating fusion images of preoperative in situ MRI and postoperative CT
of the specimen. Further studies need to prove if functional imaging may
supplement histopathological grading.
Disclosure Statement: e authors declare no conict of interest.
341
Prognostic Factors and Survival of Patients with Uterine
Sarcoma – a German unicenter Analysis
Alexandra Huß1; Mir Fuad Hasanov1; Maximilian Klar1; Baonhan Hoang1;
Ingolf Juhasz-Böss1; Michaela Bossart2
1Uniklinik Freiburg im Breisgau, medizinische Fakultät, Klinik für
Frauenheilkunde, Freiburg im Breisgau, Deutschland
2St. Josefskrankenhaus Freiburg, Gynäkologie, Freiburg im Breisgau,
Deutschland
Background: is study aimed to describe the survival and identify prog-
nostic variables in patients with uterine sarcoma (US).
Methods: is unicentric, retrospective cohort study includes 57
patients with US over 18 years treated at the Department of Obstetrics
and Gynecology at University Hospital Freiburg between 1999 and 2017.
Progression-free survival (PFS) and overall survival (OS) were calculated
and visualized in Kaplan-Meier curves. Prognostic factors for total cohort
and Leiomyosarcoma (LMS) patients were identied using log-rank test
and Cox-regression.
Result: 44 LMS, seven low grade-endometrial stromal sarcoma (LG-ESS),
four high grade-ESS and two undierentiated US patients were identi-
ed. Median age at time of diagnosis was 51.0 years (range 1883). Median
follow-up time was 35 months. PFS for the total cohort was 14.0 months
(95%-Condence-Interval (CI) 9.7-18.3) and OS 36.0 months (95%-CI
22.149.9). LG-ESS was the most favorable histological subtype (OS 150.3
months). In the multivariate analysis, patients over 52 years showed a
four times higher risk for tumor recurrence (hazard ratio (HR) 4.4; 95%-
CI 1.5-12.9). Progesterone receptor negativity was associated with a two
times higher risk for death (HR2.8; 95 %-CI 1.0-7.5). For LMS patients
age ≥52 years (p=0.04), surgical margin (p=0.01), FIGO stage (p=0.01)
and no application of chemotherapy (p=0.02) were statistically signicant
positive factors for OS.
Discussion: In this analysis, tumor histology, age at time of diagnosis
and progesterone receptor status were signicant prognostic factors for
US. Unfavorable OS in LMS patients was associated with advanced FIGO
stage, suboptimal cytoreduction and application of chemotherapy.
Conclusion: For this aggressive but rare tumor international prospec-
tive, multicenter databases are needed to provide more concordant data.
Consequent, standardized immunohistopathological workup as a basis
for molecular tumor boards is worthwhile.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
366
Personalized medicine for sarcoma patients – HERE, NOW
Manuela Regenbrecht1; Rica Sauer2; Maya Niethard3,4;
Christoph Reinhard5,6; Christian Regenbrecht5,6,7; Jürgen Loskutov6
1Helios Klinikum Berlin-Buch, Department of Oncology and Palliative Care,
Berlin, Deutschland
2Medizinisches Versorgungszentrum am Helios Klinikum Emil von Behring,
Institut für Gewebediagnostik / Pathologie, Berlin, Deutschland
3Helios Klinikum Berlin-Buch GmbH, Department for Tumor Orthopedics, Berlin,
Deutschland
4Greifswald University Hospital, Klinik und Poliklinik für Orthopädie und
Orthopädische Chirurgie, Greifswald, Deutschland
5ASC Oncology GmbH, Berlin, Deutschland
6CELLphenomics GmbH, Berlin, Deutschland
7Universitätsmedizin Göttingen, Department of Pathology, Göttingen,
Deutschland
Background: Sarcoma treatment is complicated by rarity of the disease
and its overwhelming complexity. e main therapeutical option for sar-
comas is surgery, adjuvant radiation and chemotherapy. In osteosarcoma
standard regimen has not changed over 4 decades(1, 2). Targeted thera-
peutic approaches are very limited and consist of imatinib and its analogs
in gastrointestinal stromal tumors and pazopanib(3). Overall, the current
landscape of sarcoma treatment options seems grim.
Methods:
Our group developed reverse clinical engineering approach for the sar-
comas, consisting of a robust 3D cell culture method (take rate ~80%)
and semi-automated high-throughput personalized toxicity testing(4).
is approach allows to facilitate selection of the best possible regimen
for sarcoma patients.
Result:
In close collaboration with Sarcoma Center Berlin-Brandenburg at Helios
Hospital Berlin-Buch we performed 5 personalized drug screens for the
patients with dierent types of sarcomas. e mean time between sample
processing and the test results was 37 days. For all patients we were able to
nd at least one single agent or combination, that were deemed ecient.
Discussion:
Further research and rigorous follow up is required for understanding of
the full potential of the reverse clinical engineering in sarcoma therapy.
However, even now it is obvious, that it can be used in cases with limited
options, such as clear cell sarcoma or cardiac angiosarcoma.
Conclusion:
personalized drug screens for patients with dierent sarcoma subtypes
are possible.
nding an ecient therapy regimen through reverse clinical engineer-
ing is possible.
time frame for the drug screen is permissive for the use of the reverse
clinical engineering in decision making over the sarcoma patient drug
regimen.
Indication of source:
1. N. M. Marina et al., Lancet Oncol. 17, 1396–1408 (2016).
2. S. S. Bielack et al., J Clin Oncol. 33, 2279–2287 (2015).
3. T. G. Grünewald et al., Embo Mol Med. 12, e11131 (2020).
4. K. Boehnke et al., Slas Discov. 21, 931–941 (2016).
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts232
410
A cooperative registry of the Interdisciplinary German
Sarcoma group (AIO/ARO/CAO) to optimize either neo – or
adjuvant treatment strategies for adult patients (pts) with
large sized, high grade non-rhabdomyo(soft tissue)
sarcoma (STS)
J.T. Hartmann1; H.-G. Kopp2; Volker Budach3; Viktor Grünwald4; T. Wölfel5;
T. Kluba6; M. Rudert7; P.-U. Tunn8; I. Melcher9; O. Micke1; D. Kürschner10;
R. Herbst11; B. Hertenstein12; W. Blau13; F. Mayer14; A. Serrano1; J. Groth1;
A. Kunitz9
1Katholische Hospitalvereinigung Ostwestfalen, Bielefeld,
2Robert-Bosch-Krankenhaus, Stuttgart,
3Charité - Universitätsmedizin , Berlin,
4Universität, Essen,
5Universität, Mainz,
6Städtisches Klinikum, Dresden,
7Universität, Würzburg,
8Helios Klinikum, Berlin,
9Klinikum Spandau, Berlin,
10MVZ, Delitzsch,
11Klinikum , Chemnitz,
12Klinikum Mitte, Bremen,
13Dr. Horst Schmidt Kliniken , Wiesbaden,
14Praxis und Tagesklinik, Friedrichshafen,
Background: To examine whether concomitant chemotherapy and radia-
tion (RXT) achieves sucient DFS rates for pts with high risk adult-type
STS.
Methods: is is a prospective registry (IAWS-1/-2) at 40 centers. We
included pts with conrmed high risk (size > 5cm, G2/3, deep located)
STS, at least 18 yrs of age, normal organ functions, no evidence of dis-
tant mets. ey were assigned to either (arm 1) adjuvant or neoadjuvant
(arm 2) IFO-DOXO x 3 - IFO x 2 + RXT 50.4 Gy* – IFO-DOXO x 1 (*if
indicated/applicable, otherwise IFO-DOXO x 5) consisted of DOX 60 mg/
sqm i.v., on day 1, and IFO 3 g/sqm i.v., d1-3, qd22 (d1-2, qd22 concom-
itant to RTX). Primary aim was 5-yr DFS. Sample size was calculated to
achieve a power of 80% to detect a hazard ratio of 1.388, which corre-
sponds to the dierence in DFS of 65% vs. 55% compared to historical
controls. Ecacy analysis is based on ITT population. 274 pts have to be
assessed; secondary aims: ORR (in arm B), OS, dose intensity.
Results: Between 6/09 and 10/16 292 pts were either assigned to arm
1 (n=109) or arm 2 (n=183) depending on local tumor board decision;
275 pts have been treated per protocol; median age 50 yrs (18-70); m/f
56/44%; ECOG 0/1/2, 67/21/3%; location, extr/rp/centr/HNO/girdle,
53/21/12/6/4%; histo, pleoNOS/LS/other/SS/LMS, 28/20/15/11/11%; G
2/3, 29/70%; deep, 100%; med. Size, 9.5 cm; resection, n.d. 3.6%; R-status,
R0/1/2/unknown, 80/12/1/3%. 91 resp. 90% of pts underwent at least 3
cyc of DOX/IFO with higher dose reduction necessary due to IFO toxicity.
Discontinuation rate of CTX was 5.5%. RTX was applicable in 71% of pts.
Med. duration of f/u was 26.3 mos (0.9-165.6). 29.8% pts relapsed. 5-yr
DFS was 61.7% (95% CI: 49.6-73.9%) in arm 1 and 53.1% (95% CI: 41.3-
64.9%) in arm 2 with less events being observed during yrs 5-10. 5-yr OS
was 79.2% (95% CI: 68.9-89.6%) in arm 1 and 68.2% (95% CI: 57.4-78.6%)
in arm 2. Tumor reduction was seen in 52% of pts in arm 2.
Conclusions: CTX in close conjunction with RTX is an eective and fea-
sible approach in STS population when limited to high risk pts.
Indication of source: ESMO 2021
Disclosure Statement: e authors declare no conict of interest.
450
Value of local treatment modalities in patients with localized
Ewing Sarcoma. Report from the Ewing 2008 trial
Philip Heesen1,2; Andreas Ranft3,4; Vivek Bhadri5; Benedicte Brichard6;
Stephane Collaud4,7; Sona Cyprova8; Hans Eich9; Torben Ek10;
Hans Gelderblom11; Jendrik Hardes4,12; Lianne Haveman13;
Wolfgang Hartmann14; Peter Hauser15; Heribert Jurgens16; Jukka
Kanerva17; Thomas Kühne18; Anna Raciborska19; Jelena Rascon20;
Arne Streitbürger4,12; Beate Timmermann4,21; Yasmine Uhlenbruch22;
Uta Dirksen3,4
1University of Zurich, Faculty of Medicine
2University of Duisburg Essen, Pediatrics III
3University Hospital Essen, West German Cancer Center, Pediatrics III
4German Cancer Consortium, Partnersite Essen
5University of Sydney, Australia Faculty of Medicine and Health, Chris O´ Brien
Lifehouse
6Université Catholique de Louvain, Department of Pediatric Haematology and
Oncology
7University Hospital Essen, Department of Thoracic Surgery
8Motol Children´s Hospital, Charles University
9University Hospital Muenster, Radiotherapy and Radiooncology
10Queen Silvia Children´s Hospital, Childhood Cancer Center
11Leiden University Medical Center, Department of Medical Oncology
12University Hospital Essen, Clinic of Orthopedics
13Princess Máxima Center for Pediatric Oncology, Department of Solid tumors
14University Hospital Muenster, Gerhard Domagk Institute for Pathology
15Borsod-Abaúj-Zemplén County University Teaching Hospital, Velkey László
Child’s
16University Childrens Hospital Münster, Department of Pediatric Hematology
and Oncology
17HUS Helsinki University Hospital, New Children´s Hospital, Div. Hematology
and Stem Cell Transplantation
18University Children´s Hospital Basel
18 Department of Oncology/ Haematology, Basel,
19Mother and Child Institute, Department of Oncology and Surgical Oncology
for Children and Youth
20Vilnius University Hospital Santaros Klinikos, Center for Pediatric Oncology
and Hematology
21University Hospital Essen, Clinic for Particle Therapy, West German Proton
Beam Centre
22St. Josefs Hospital Bochum, University Hospital, Patient representative
Purpose: Local treatment is an essential element in the multimodal treat-
ment of Ewing sarcoma (EWS). e choice of a local control modality
for EWS is still controversial. Aim of our study was to analyze the impact
of local treatment modalities and clinical variables on overall survival in
patients treated according to the Ewing 2008 protocol.
Methods: e prospectively collected data of 833 patients with localized
EWS treated in the Ewing 2008 trial between 2009 and 2018 were analyzed.
All patients received induction chemotherapy prior to local treatment. We
tested proportional hazards assumption using Schoenfeld-residuals and
Goodness-of-t test, hazard ratios (HRs) with 95% Condence Intervals
were calculated using Cox regression. Log-rank test was performed.
Results: e 5-year survival probabilities were 0.84 (0.79, 0.89) for sur-
gery, 0.77 (0.69, 0.86) for radiotherapy and 0.84 (0.79, 0.88) for combina-
tion of surgery & radiotherapy, p=0.12.
e HR of radiotherapy vs surgery alone or combination of surgery and
radiotherapy was 1.23 (0.66, 2.30) for patients that had a small tumor vol-
ume (<200 mL) and 1.76 (0.90, 3.45) for patients that had a large tumor
volume (≥ 200 mL), aer adjusting for known prognostic factors as age
and tumor site. Detailed analysis of local treatment modalities in dierent
sites will be presented.
Discussion: OS was better in patients treated with surgery or surgery &
radiotherapy compared to radiotherapy alone, but this dierence was not
statistically signicant. OS might be increased in patients with large tumor
volume when treated with surgery or a combination of surgery & radio-
therapy compared to radiotherapy only.
Conclusions: Surgery and surgery & radiotherapy might be superior to
radiotherapy only. Treatment plans should consider our ndings, in line
with patient- characteristics and -preferences.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 233
593
There is no evidence for clinically relevant needle tract
seeding or abdominal recurrence following pre-treatment
biopsy of gastrointestinal stromal tumors (GIST) – results of a
systematic review
Jens Jakob1; Rashad Salameh2; David Wichmann1; Nicos Charalambous1;
Anne-Christine Zygmunt1; Michael Ghadimi1; Judith Heinz3; Ulrich
Ronellentsch4
1Universitätsmedizin Göttingen, Klinik für Allgemein-, Viszeral und
Kinderchirurgie
2Universitätsklinikum Carl Gustav Carus, Klinik und Poliklinik für Viszeral-, Thorax
und Gefäßchirurgie
3Universitätsmedizin Göttingen, Institut für Medizinische Statistik
4Universitätsklinikum Halle , Klinik für Viszerale, Gefäß und endokrine Chirurgie,
Halle (Saale), Deutschland
Background: No clear consensus exists if pre-treatment biopsy leads to
needle tract seeding or increase abdominal recurrence of GIST. e objec-
tive of this study was to estimate the risk of tumor recurrence associated
with pre-treatment core needle biopsy OR ne needle aspiration of gastro-
intestinal stromal tumors.
Methods: We performed a systematic literature search and included stud-
ies assessing the clinical and oncological outcome of GIST-patients who
underwent a pre-treatment core needle biopsy or ne needle aspiration.
We assessed methodological quality with the Newcastle-Ottawa-Scale for
non-randomized studies.
Results: Four non-randomized studies and seven case reports comprising
174 patients were eligible for inclusion. Needle tract seeding or abdominal
recurrence aer pre-treatment biopsy were primary endpoints in only two
trials. ere was no documentation of a single case of needle tract seeding.
None of the studies reported an increased rate of abdominal recurrence
aer pre-treatment biopsies.
Conclusion: ere appears to be no clinically relevant risk of needle tract
seeding or increased abdominal recurrence aer pre-treatment biopsy of
GIST.
Disclosure Statement: e authors declare no conict of interest.
628
DNA methylation-based classier and gene expression
signatures detect BRCAness in osteosarcoma
Maxim Barenboim1; Michal Kovac2; Baptiste Ameline3; David Jones4; Olaf
Witt5; Stefan Bielack6; Stefan Burdach7; Daniel Baumhoer3; Michaela
Nathrath8
1Technical University of Munich, Klinikum rechts der Isar, Department of
Pediatrics and Children’s Cancer Research Center, Munich, Deutschland
2Slovak University of Technology, Faculty of Informatics and Information
Technologies, Bratislava, Slovakia
3University of Basel, University Hospital Basel, Bone Tumour Reference Centre at
the Institute of Pathology, Basel, Schweiz
4Hopp Childrens Cancer Center Heidelberg (KiTZ), Heidelberg, Deutschland
5University Hospital Heidelberg, Department of Pediatric Oncology,
Hematology and Immunology, Heidelberg, Deutschland
6Klinikum Stuttgart – Olgahospital, Stuttgart Cancer Center, Pediatrics 5
(Oncology, Hematology, Immunology), Stuttgart, Deutschland
7Technical University of Munich, Institute of Pathology, Childrens Cancer
Research Center - Department of Pediatrics , Munich, Deutschland
8Klinikum Kassel, Department of Pediatric Oncology, Kassel, Deutschland
Background: Osteosarcoma (OS) is the most common primary malig-
nant bone tumour. BRCAness is a phenotypical trait in tumors with defect
in homologous recombination (HR) repair resembling tumors with inac-
tivation of BRCA1/2 rendering these tumors sensitive to poly-(ADP)-ri-
bose polymerase inhibitors (PARPi). Recently, OS was shown to exhibit
molecular features of BRCAness. Our goal was to develop a method com-
plementing existing genomic methods to aid clinical decision making on
administering PARPi in OS patients.
Methods: OS samples with DNA-methylation data were divided to
BRCAness-positive and negative groups based on degree of their genomic
instability (n=41). Methylation probes were ranked according to decrease
variance dierence between two groups. Top 2000 probes were selected
for training and cross-validation of random forest (RF) algorithm. Two
third of available OS RNA-Seq samples (n=17) from the top and bottom
of sample list ranked according to genome instability score were subjected
to dierential expression (DE) and, subsequently, to gene set enrichment
analyses (GSEA).
Result: Combined accuracy of trained RF was 85% and the average of area
under the ROC curve was 0.95. ere were 449 upregulated and 1,079
downregulated genes in BRCAness-positive group (fdr<0.05). GSEA
of upregulated genes detected enrichment of DNA replication and, of
note, mismatch repair and HR signatures (FWER<0.05). Validation of
BRCAness classier with independent OS set (n=20) showed AUC of 0.87
with accuracy of 90%.
Discussion: e RF classier can identify BRCAness cost-eective since
it does not require sequencing of control tissue DNA. HR gene expres-
sion signature was identied for the rst time in OS. e low frequency
of BRCA1/2 mutations in OS implies that the increased presence of
BRCAness in OS arises from alterations in other genes of the HR pathway.
Conclusion: We developed a new classier based on DNA-methylation
patterns that detects BRCAness in OS samples with high accuracy. is
approach can be extended to cancers characterized by genome instability
(PMID: 34762643).
Disclosure Statement: e authors declare no conict of interest.
749
Convergent genetic mechanisms drive EIF4EBP1
overexpression, translational deregulation and tumorigenesis
in Ewing sarcoma
Cornelius Funk1,2; Martin F. Orth3; Karim Aljakouch4; Jing LI1,2;
RolandImle2,5; Laura Romero-Perez1,2; Tilman L. B. Hölting3;
Maximilian M. L. Knott3; Aruna Marchetto3; Felina Zhanow1,2; Ana Sastre6;
Javier Alonso7,8; Rainer Will9; Felix Bestvater10; Thomas Kirchner3;
Olaf Witt2,11; Ina Oehme2,11; Ana Banito2,5; Gabriel Leprivier12;
Wolfgang Hartmann13; Uta Dirksen14; Stefan M. Pster2,15;
Jeroen Krijgsveld4; Florencia Cidre-Aranaz1,2; Thomas G.P. Grünewald1,2,3;
Julian Musa1,2,16
1Deutsches Krebsforschungszentrum, Division of Translational Pediatric
Sarcoma Research, Heidelberg, Deutschland
2Hopp Childrens Cancer Center (KiTZ), Heidelberg, Deutschland
3Institute of Pathology, Faculty of Medicine, LMU Munich, Max-Eder Research
Group for Pediatric Sarcoma Biology, München, Deutschland
4Deutsches Krebsforschungszentrum, Proteomics of Stem Cells and Cancer,
Heidelberg, Deutschland
5Deutsches Krebsforschungszentrum, Soft-Tissue Sarcoma Junior Research
Group, Heidelberg, Deutschland
6Hospital Infantil Universitario La Paz, Unidad hemato-oncología pediátrica,
Madrid, Spanien
7Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid,
Spanien
8Instituto de Investigación de Enfermedades Raras, Unidad de Tumores Sólidos
Infantiles, Madrid, Spanien
9Deutsches Krebsforschungszentrum, Genomics & Proteomics Core Facilities
TP3, Heidelberg,
10Deutsches Krebsforschungszentrum, Light Microscopy Facility (W210),
Heidelberg, Deutschland
11Deutsches Krebsforschungszentrum, Pediatric Oncology (B310), Heidelberg,
Deutschland
12Institute of Neuropathology, Medical Faculty, University Hospital Düsseldorf,
Düsseldorf, Deutschland
13Division of Translational Pathology, Gerhard-Domagk Institute of Pathology,
University Hospital of Münster, Münster, Deutschland
14Department of Pediatric Hematology and Oncology, University Hospital of
Essen, Essen, Essen, Deutschland
15Deutsches Krebsforschungszentrum, Division of Pediatric Neuro-Oncology,
Heidelberg, Deutschland
16Universitätsklinikum Heidelberg, Department of General, Visceral and
Transplantation Surgery, Heidelberg, Deutschland
Background: Ewing sarcoma (EwS) is an aggressive pediatric bone can-
cer characterized by a chromosomal translocation fusing the EWSR1 gene
to various members of the ETS family of transcription factors – most
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts234
commonly FLI1. EWSR1-FLI1 acts as an oncogenic transcription factor
driving EwS malignancy. Additional mutations in EwS are rare, however
50% of EwS cases include gains of chr8. EIF4EBP1, a major mTORC1
downstream target and chr8 gene, encodes for a translation initiation fac-
tor with controversial roles in tumorigenesis.
Methods: Using a variety of bioinformatic analyses and functional in vitro
and in vivo experiments and pSILAC mass spectrometry, we characterized
EIF4EBP1 in EwS.
Result: Screening a microarray gene expression dataset of 196 EwS tumors
with matched clinical data, we identied EIF4EBP1 as the one being most
strongly associated with patients´ overall survival among all chr8 genes.
Silencing of EWSR1-FLI1 in 14 EwS cell lines led to a downregulation of
EIF4EBP1, which was validated in vivo. Knockdown of EIF4EBP1 lead to
signicantly decreased cell proliferation, 2D clonogenic and 3D anchor-
age-independent growth of EwS cell lines and similarly reduced growth
of EwS xenogras. Proteomic proling using pSILAC mass spectrome-
try in EIF4EBP1 silenced EwS cell lines identied dierentially expressed
proteins being strongly enriched in respiratory chain and oxidative phos-
phorylation proteins.
Discussion: Our data clearly supports an oncogenic role of EIF4EBP1
in EwS and highlights the hitherto not suciently appreciated aspect of
translational deregulation in Ewing sarcomagenesis. Moreover, our study
highlights the EIF4EBP1-mediated prognostic relevance of chr8 gains in
EwS.
Conclusion: EIF4EBP1 is a prognostically relevant gene, which is upregu-
lated in EwS by both, EWSR1-FLI1 and chr8 gains and which contributes
to proliferation and clonogenic growth of EwS cells in vitro and in vivo,
likely due to translational deregulation of proteins involved in oxidative
phosphorylation.
Disclosure Statement: e authors declare no conict of interest.
765
Eects of an individualized exercise intervention on gait
function in adolescents and young adults (AYA) with tumor
endoprosthesis of the lower extremity - a pilot RCT (proGAIT)
Simon Basteck1,2; Wiebke Guder3; Uta Dirksen1,2; Arno Krombholz4;
Miriam Götte1,2
1Universitätsklinikum Essen, Westdeutsches Tumorzentrum, Klinik für
Kinderheilkunde 3
2Deutsches Konsortium für Translationale Krebsforschung, Standort Essen
3Universitätsklinikum Essen, Klinik für Tumororthopädie und Sarkomchirurgie
4Ruhr-Universität Bochum , Fakultät für Sportwissenschaft
Background: Limb preservation using endoprosthesis in bone tumor
patients is in some cases contrasted by signicant functional limitations
and gait abnormalities. Primary aim of the proGAIT-RCT was to evaluate
the eectiveness of an exercise intervention on gait function in AYA can-
cer survivors with tumor endoprosthesis.
Methods: N = 11 cancer survivors with a mean age of 26.6. (±8.4) years
and a mean follow-up since tumor endoprosthesis implantation around
the knee of 4.9 (±4.9) years were randomized to an intervention group
that received a partially supervised individualized 8-week exercise pro-
gram or a control group. Gait function was assessed via 3D gait analy-
sis. Secondary outcomes were QoL, fatigue, and functional performance
assessed via questionnaires and functional tests.
Results: e exercise intervention had small to medium eects on gait
score GDI |d|=0.50 (unaected leg), |d|=0.24 (aected leg), subjective
functional scores TESS |d| = 0.74 and MSTS |d| = 0.49 and functional
tests TUG and TUDS |d| = 0.61 and|d| = 0.52. Fatigue changed in favor
of the control group (|d| = 0.85). None of these changes showed statistical
signicance. No adverse events occurred.
Discussion: Promising intervention eects lead to the assumption that
exercise interventions could make an important contribution to improve
lower limb function and patient related outcomes in AYA cancer survivors
with tumor endoprosthesis. Because of the small sample size in this pilot
study, none of the changes were signicant.
Conclusion: e proGAIT study addresses a relevant research gap and
probably initiates a powered RCT as a follow-up project. Particular eorts
should be made to improve exercise-related follow-up care for aected
patients.
Disclosure Statement: e authors declare no conict of interest.
801
Multipel rezidivierendes und kurativ wiederholt reseziertes
retroperitoneales Liposarkom - 20 Jahre nach Erstdiagnose
bei stabiler pathohistologischer Morphe jedoch wechselndem
Grading (außergewöhnlicher Fallbericht)
Regina Moritz-Tugral1; Hans-Ulrich Schulz2; Dörthe Jechorek1;
Frank Meyer3
1Institut für Pathologie, Universitätsklinikum Magdeburg A.ö.R., Magdeburg,
Deutschland
2Klinik für Allgemein- und Viszeralchirurgie, AMEOS-Klinikum Haldensleben,
Haldensleben, Deutschland
3Klinik für Allgemein-, Viszeral-, Gefäß- und Transplantationschirurgie,
Universitätsklinikum Magdeburg A.ö.R., Magdeburg, Deutschland
Ziel: Illustration d. außergewöhnl. Casus eines retroperit. Liposarkoms,
welches trotz init. R0-Resektion vor 20 Jahren mehrfach rezidivierte
(Tumor[Tu]-Manifestationen: n=18). Der seltene langfristig-klin.
Verlauf wurde anhand d. diagnost. sowie pathomorphol. & histol.
Tu-Eigenschaen sowie der jeweiligen Spezikationen d. jeweils nur mit-
telfristig Tu-freien “Outcomes” aufgearbeitet.
Kasuistik: Ein inzw. 70-jähriger Mann wurde inital mit einem
23x29x15 cm großen retroperit. Liposarkom links diagnostiziert & b.
Ersteingri R0-reseziert.
In der Tu-Nachsorge wurden insges. 14 retro- & 4 intraperit.
Tu-Rezidive innerhalb v. 10 Episoden eines erneut aufgetretenen
Tu-Wachstums (durchschnittl. Tu-freie Zeitdauer: 20,04 [range: 12,64–
36,04] Monate) diagnostiziert. Bei allen Folgeeingrien konnte stets in
kurativer Intention überwiegend R0-reseziert bzw. im Folgeeingri –
nachreseziert werden. Die durchschnittl. Präparategröße betrug 8,065
(range: 1,7–29)cm.
Die Histologie zeigte initial ein Liposarkom G3 - b. den Tu-Rezidiven
bestätigte sich jeweils das Liposarkom (variierendes G). Durch das
teils verdrängende Tu-Wachstum wurden mehrfach auch multivisz.
Resektionen d. paarigen & unpaaren Bauchorgane notw., wobei der-
zeit eine chron., Tu-resezierend induz. enterokut. Fistel nach letzter
Tu-Resektion vor >12Monaten vorliegt (mit Colostomabeutel versorgt).
Schlussfolgerung: Die chir. Resektion unter kurativer Intention ist auch b.
Liposarkomrezidiv eine aussichtsreiche er.-Option, da b. jeweils errre-
ichtem R0-Status auch b. multipel rekurrentem Liposarkom ein mittel- bis
langfristiges, Tu-therapeut. beherrschbares Outcome mit signif. Tu-freien
Perioden erreicht werden kann. Dies wird eindrucksvoll & erstmals in
einer deratigen Eingris- & Präparateserie im vorgest. spektakulären
Fall demonstriert. Bei dieser Sarkomentität erscheint das Tu-Rezidiv-
assoziierte, prognost. eher günstigere G1/G2 diesen Langzeitverlauf zu
begünstigen. Eine engmaschige kiln. & bildgebende Tu-Nachsorge ist
hierfür unerlässlich.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 235
Skin Cancer including Melanoma
Poster
73
Encorafenib plus binimetinib in patients with locally
advanced, unresectable or metastatic BRAFV600-mutated
melanoma: an ongoing multi-centric, multi-national,
prospective, longitudinal, non-interventional
study – BERING-Melanoma
Dirk Schadendorf1; Erika Richtig2; Carmen Loquai3; Andrea Forschner4;
Ralf Gutzmer5; Sebastian Haferkamp6; Jochen Utikal7;
Jessica Cecile Hassel8; Friedegund Meier9; Dirk Debus10; Michael Fluck11;
Daniela Goeppner12; Helmut Kehrer13; Reinhard Dummer14;
Roger von Moos15; Jan Thompson16; Laura Gengenbacher17;
Olivier Michielin18; Christoph Hoeller19
1Department of Dermatology, University Hospital Essen, Essen, Deutschland
2Department of Dermatology, University of Graz, Graz, Österreich
3Department of Dermatology, University Medical Center Mainz, Mainz,
Deutschland
4Department of Dermatology, University Hospital of Tuebingen, Tuebingen,
Deutschland
5Department of Dermatology, Mühlenkreiskliniken Minden, Ruhr University
Bochum, Minden, Deutschland
6Department of Dermatology, University Hospital of Regensburg, Regensburg,
Deutschland
7Skin Cancer Unit, DKFZ and Medical Faculty Mannheim of Heidelberg
University, Mannheim, Deutschland
8Department of Dermatology, Heidelberg University Hospital, NCT Heidelberg,
Heidelberg, Deutschland
9Department of Dermatology, University Hospital Carl Gustav Carus, Dresden,
Deutschland
10Department of Dermatology, Nuremberg General Hospital, Paracelsus Medical
University, Nuremberg, Deutschland
11Department of Internal Medicine, Fachklinik Hornheide, Muenster,
Deutschland
12Department of Dermatology, University Hospital of Giessen, Giessen,
Deutschland
13Department of Dermatology, Ordensklinikum Linz Elisabethinen, Linz ,
Österreich
14Department of Dermatology, University Hospital of Zurich, Zurich, Schweiz
15Department of Medical Oncology, Kantonsspital Graubuenden, Chur, Schweiz
16Alcedis GmbH, Giessen, Deutschland
17Pierre Fabre Pharma GmbH, Freiburg, Deutschland
18Center of Personalized Oncology, Lausanne University Hospital (CHUV),
Lausanne, Schweiz
19Department of Dermatology, Medical University of Vienna, Vienna, Österreich
Background: For the treatment of locally advanced, unresectable or met-
astatic BRAFV600-mutated melanoma, targeted therapy with a combina-
tion of BRAF and MEK inhibitors represents a standard of care.
e combination therapy of encorafenib plus binimetinib was approved
in the EU in Sep 2018 and in Switzerland in Nov 2019. e approval was
based on positive results from the COLUMBUS study, with a median pro-
gression-free survival (PFS) of 14.9 mo (5-year PFS: 23%) and a median
overall survival (OS) of 33.6 mo (5-year OS: 35%). e observed tolerabil-
ity prole consisted of the expected adverse events of this substance class.
Methods: BERING-Melanoma is an ongoing, multi-national, multi-cen-
tric, prospective, longitudinal, non-interventional study (NIS). e proj-
ect aims to enroll up to 750 patients at a total of 80 German, Austrian and
Swiss sites with a total study duration of approx. 8 yrs. From Oct 2019 to
mid Apr 2022, 308 patients have been included.
Result: e NIS analyses the ecacy, quality of life, safety and tolerability
of treatment with encorafenib + binimetinib in advanced, unresectable
or metastatic BRAFV600-mutated melanoma under real-world condi-
tions. e study focuses on the documentation of rst- and second-line
treatment (i.e. aer one line of prior checkpoint inhibition therapy in the
advanced setting) and patients treated according to the SmPC (Summary
of Product Characteristics). e primary objective is to collect data on the
1-year PFS rate. In addition, the inuence of prognostic factors on ecacy,
safety and tolerability is investigated.
Discussion: Since data from controlled clinical trials are based on a
selected patient population, the present NIS investigates the use of
encorafenib + binimetinib under real-world conditions in a broader
patient population.
Conclusion: At this year’s DKK Congress, the inclusion process as well as
current data on the baseline characteristics of the included patients will be
presented. e NIS is sponsored by Pierre Fabre Pharma.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
267
Use of nivolumab (NIVO) in adjuvant melanoma patients:
real world data from NICO, a national prospective non-
interventional study
Ralf Gutzmer1; Peter Mohr2; Thomas Eigentler3; Imke Grimmelmann4; Lisa
Zimmer5; Elisabeth Livingstone5; Selma Ugurel5; Jochen Utikal6; Verena
Müller6; Daniela Göppner7; Rudolf Herbst8; Alexander Kreuter9; Claudia
Pföhler10; Wiebke Hollburg11; Loquai Carmen12; Martin Herber13; Katharina
C. Kähler14; Michael Weichenthal14; Dirk Schadendorf5
1Mühlenkreiskliniken AöR, Universitätsklinikum der Ruhr-Universität, Minden,
Deutschland
2Elbe-Kliniken Buxtehude, Buxtehude, Deutschland
3Charité - Universitätsmedizin Berlin, Klinik für Dermatologie, Venerologie und
Allergologie, Berlin, Deutschland
4Medizinische Hochschule Hannover, Haut-Tumor-Zentrum, Hannover,
Deutschland
5Universitätsklinikum Essen, Essen, Deutschland
6Deutsches Krebsforschungszentrum (DKFZ) und Universitätsklinikum
Mannheim, Ruprecht-Karl Universität Heidelberg, Mannheim,
7Justus-Liebig-Universitat Gießen, Gießen, Deutschland
8Helios Klinikum Erfurt, Erfurt, Deutschland
9Helios St. Elisabeth Klinik, Oberhausen, Deutschland
10Universitätsklinikum des Saarlandes, Homburg/Saar, Deutschland
11Hämatologisch-Onkologische Praxis Altona (HOPA), Hamburg, Deutschland
12Universitätsmedizin Mainz, Hautkrebszentrum Rhein-Main, Mainz,
Deutschland
13Bristol Myers Squibb, München, Deutschland
14Universitätsklinikum Schleswig-Holstein, Kiel, Deutschland
Background: e phase 3 CM 238 trial demonstrated durable clinical
benet for NIVO in patients with resected stage III B/C or IV melanoma,
and NIVO has become a standard treatment for resected melanoma.
Additional real-world data on eectiveness and tolerability are warranted
and are collected in NICO, a prospective, non-interventional study in
Germany associated to ADOREG.
Methods: NICO (NCT02990611) consists of 3 cohorts: patients with
either advanced melanoma who started therapy with NIVO+IPI or NIVO
(cohort 1 and 2) or patients with resected Stage III/IV melanoma treated
with NIVO in the adjuvant setting (cohort 3). Patients in all cohorts are
followed for up to 5 years. Relapse-free survival is the primary objective
for cohort 3. We report data from the second interim analysis of cohort 3
(database lock: 31 January 2022) focusing on baseline patient character-
istics and safety.
Result: Baseline data were available for 331 patients in cohort 3. Median
age of patients was 64 years (range, 23-94), and 59% were male. Almost all
patients (92%) had ECOG score < 2 (8% unknown), and 9%, 30%, 44%,
2% and 13% had stage IIIA, IIIB, IIIC, IIID, and IV disease (AJCC, 8th
edition), respectively. At initial diagnosis, 27% of patients enrolled in this
study had BRAF mutant melanoma, and 52% had BRAF wildtype (21%
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts236
unknown). To date, 346 treatment-related adverse events (TRAE) were
reported [grade 1/2: 273 (79%); grade 3: 45 (13%); grade 4: 11 (3,2%);
grade 5: 1 (< 1%); missing grade: 16 (4,6%)]. At least one non-serious
treatment-related AE was reported in 129 (39,1%) patients, and one seri-
ous TRAE in 42 (12,7%) patients. 13,9% of patients discontinued due to
TRAE. Median time on study is 18,2 months (11.9-12.7), and 8,8% of the
patients are still on treatment.
Discussion: is study of adjuvant NIVO treatment in a real-world set-
ting supports the known safety prole of NIVO in a less selected patient
population compared to clinical trials. Preliminary data on AE occurrence
reect the known NIVO safety prole.
Conclusion: is data provides valuable insight in the current use of
NIVO in the adjuvant setting.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
544
Retrospective Single Case Reports on the Treatment of
Advanced BRAFV600-mutated Malignant Melanoma with
Encorafenib plus Binimetinib (REMINISCENCE)
Dirk Debus1,2; Mareike Alter1; Marie-Therese Dernoscheg2; Peter Rohrer2;
Lukas Koch2; Van Anh Nguyen3; Patrick Terheyden4
1Universitätshautklinik, Universitätsklinikum Magdeburg, Magdeburg,
Deutschland
2Universitätsklinik für Dermatologie & Venerologie, Medizinische Universität
Graz, Graz, Österreich
3Universitätsklinik für Dermatologie, Venerologie & Allergologie, Medizinische
Universität Innsbruck, Innsbruck, Österreich
4Klinik für Dermatologie, Allergologie & Venerologie, Universitätsklinikum
Schleswig-Holstein, Lübeck, Deutschland
Background: Challenges for the treatment of advanced, unresectable or
metastatic BRAFV600 mutated melanoma include the denition of an opti-
mal therapy sequence. is project aims to collect case reports of patients
(pts) with remarkable treatment courses for training purposes and scien-
tic discussion.
Methods: Cases of adult pts with advanced, unresectable or metastatic
BRAFV600 mutated melanoma with a therapy sequence including ongo-
ing or completed encorafenib/binimetinib (EB) were selected by treating
physicians. Aer written informed consent data of eligible pts were docu-
mented retrospectively using standardized case report forms.
Result: In total, 17 pts from 5 centers in Germany and Austria were
included. Five cases will be presented: 1) female, 64 yrs, long-lasting com-
plete response (CR) under 1st-line EB therapy in the metastatic setting
(treatment duration [TD] at cut-o: 5.6 yrs); 2) male, 53 yrs, advanced
setting including brain metastases, complex prior therapy lines, EB in
late therapy line with partial response (PR) and parallel CNS surgery (TD
at cut-o: 1.4 yrs); 3) female, 82 yrs, poor prognosis (brain metastasis,
increased LDH and concomitant autoimmune disease), 1st-line EB ther-
apy with PR aer surgical intervention and stereotactic radiotherapy (TD
at cut-o: 1 yr); 4) female, 88 yrs, diverse (oncologic) concomitant dis-
eases, initial curative approach, EB therapy in 1st-line in the advanced
setting with CR and adequate tolerability limited to mainly gastrointesti-
nal side eects (TD at cut-o: 1.1 yrs); 5) female, 71 yrs, increased LDH,
2nd-line EB therapy with stable PR (TD at cut-o 1.2 yrs) following rapid
progression under rst-line nivolumab therapy.
Discussion: ese insights into clinically relevant therapeutic approaches
could serve to establish a basis for discussion on therapy management and
sequence between medical experts.
Conclusion: All 5 patients presented with heterogenous therapy courses
and show a relevant therapy benet along with adequate tolerability
during EB therapy.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
648
First results of a clinical study investigating hearing and
hearing impairment in melanoma patients under therapy with
checkpointinhibitors or BRAF and MEK inhibitors
Claudia Pföhler1; Julia Ehrmann1; Roman Saternus1; Anne-Catherine
Wagner1; Krista Yordanova1; Leonie Adam1; Bernhard Schick2;
Thomas Vogt1; Gentiana I. Wenzel2
1Universitätsklinikum des Saarlandes, Klinik für Dermatologie
und Hauttumorzentrum, Homburg/Saar, Deutschland
2Universitätsklinikum des Saarlandes, Klinik für Hals-, Nasen- und
Ohrenheilkunde, Homburg,
Background: Checkpointinhibitors (CPI) may lead to immune-related
side eects (irAEs). e development of some irAEs such as therapy-in-
duced vitiligo could be associated with clinical benet in the context of
CPI treatment. CPI treatment may also lead to the production of anti-
bodies against retinal or inner ear antigens inducing impairment of vision
and hearing as described previously. Patients with vitiligo may suer from
hearing impairment resulting from an aection of pigmented cells in the
inner ear.
Methods: We investigated 93 melanoma patients (m=57, f=36, median
age 64 years) who received nivolumab (n=37), pembrolizumab (n=28),
a combination of ipilimumab and nivolumab (n=3) or a combination
of BRAF- /MEK inhibitors (n=14) due to stage III or IV melanoma. All
patients received audiometric assessment. 27 patients received a re-test.
Results: 15/93 of the patients reported an already diagnosed hearing
impairment that could be veried by audiometry. We diagnosed in 60/93 a
so far unknown hearing impairment and only 18/93 had normal hearing.
13/93 patients developed therapy-induced vitiligo. From 27 patients that
were re-tested, six presented a sensorineural hearing loss of at least 10 dB
in at least one frequency at and above 3 KHz. Out of these one case was
aected bilaterally in the rest of 5 were aected just single sided.
Discussion: e high number of melanoma patients with unknown
hearing impairment is noticeable. However, it remains unclear if hearing
impairment results from melanoma disease or its treatment or if hearing
impairment is basically underdiagnosed in this population group. It is
imaginable that therapy-induced vitiligo is associated with the develop-
ment of hearing impairment.
Conclusion: Further studies are warranted to investigate hearing before,
under and aer therapy with CPI or BRAF-/MEK inhibitors. is might
allow to recognize early and monitor the evolution of therapy-induced
hearing impairment as well as to assess possible adjustments of therapeutic
regimens.
Disclosure Statement: e authors declare the following: CP received honoraria
(speaker honoraria or honoraria as a consultant) and travel support from Novartis,
BMS, Roche, Merck Serono, MSD, Celgene, AbbVie, SUNPHARMA, Pierre Fabre
and LEO
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 237
959
Chernobyl‘s Aftermath: Multiple manifestations of basalioma
in a patient after radioactive contamination in 1986
Marcel Ebeling1; Konrad Steinestel2; Michael Grunert3; Frank Wilde4
1German Armed Forces Hospital Ulm, Department of Oral and Plastic
Maxillofacial Surgery, Ulm, Deutschland
2German Armed Forces Hospital Ulm, Institute of Pathology and Molecular
Pathology, Ulm, Deutschland
3German Armed Forces Hospital, Department of Nuclear Medicine, Ulm,
Deutschland
4University Hospital Ulm, Department of Oral and Plastic Maxillofacial Surgery,
Ulm, Deutschland
Background: e Chernobyl nuclear disaster is considered the worst
nuclear accident in history. In 1986, two explosions at the reactor in
Pripyat, Ukraine resulted in the destruction of the reactor core and unhin-
dered release of radioactive particles. Radioactivity is a risk factor for the
development of basal cell carcinoma (BCC), since radiation-induced
mutations in both Sonic hedgehog (Shh) signaling pathway genes and
TP53 have been described.
Methods: We present the case of a patient with a history of radiation
exposure upon the 1986 Chernobyl accident who presented to our outpa-
tient clinic with recurrent BCCs in the facial region.
Result: e patient presented to our clinic with two facial lesions suspi-
cious for BCC. Although there were no typical risk factors, yet 11 BCCs
had previously been removed. Staging using an 18F-FDG-PET/CT as well
as ultrasound of the abdomen revealed no other tumor manifestations,
except for a lymph node which showed no signs of malignancy upon ne
needle biopsy.Diagnostic excision of the two facial lesions was performed,
and histopathological workup revealed BCC at the right temporal region
and acanthopapillomatosis at the corner of the mouth. Aer presentation
to the tumor board, complete resection of the basal cell carcinoma was
initiated. e patient remains attached to our hospital for follow-up.
Discussion: Despite contradictory studies, there are clear indications that
radioactive radiation must be assumed to play a role in the development
of BCCs. is must be considered due predisposing factors such as muta-
tions in the PTCH gen, p53 mutations, chronic exposure to UV radiation,
or autosomal dominant inherited tumor syndromes such as Gorlin-Goltz
syndrome.
Conclusion: is case demonstrates the value of early use of 18F-FDG-
PET/CT in staging/restaging to visualize BCC location, local spread,
potential metastases, secondary tumors and to aid in the decision of ther-
apeutic management. Furthermore, it underlines that long-term eects of
ionizing radiation should be considered in the diagnosis and management
of malignant skin tumors.
Disclosure Statement: e authors declare no conict of interest.
Supportive Care
Best-of-Abstract-Vortrag
356
Eects of a specic strength training on self-reported
activities of daily living, physical activity and motor
performance among children and adolescents with leukemia
or non-Hodgkin lymphoma: ndings of the randomized
controlled ActiveADL Study
Dominik Gaser1,2; Christiane Peters2; Renate Oberhoer-Fritz2; Miriam
Götte3; Irene Schmid4; Tobias Feuchtinger4; Irene Teichert-von Lüttichau1;
Sabine Kesting1,2
1Kinderhämatologie und –Onkologie, Kinderklinik München Schwabing,
Klinik und Poliklinik für Kinder- und Jugendmedizin, Klinikum rechts der Isar,
Technische Universität München, München, Deutschland
2Lehrstuhl für Präventive Pädiatrie, Fakultät für Sport- und
Gesundheitswissenschaften, Technische Universität München, München,
Deutschland
3Pädiatrische Hämatologie und Onkologie, Klinik für Kinderheilkunde III,
Universitätsklinikum Essen , Essen, Deutschland
4Zentrum für Pädiatrische Hämatologie und Onkologie, Kinderklinik und
Kinderpoliklinik im Dr. von Haunerschen Kinderspital, Klinikum der Universität
München, München, Deutschland
Background: Due to treatment- and disease-related side eects, chil-
dren undergoing cancer treatment show reduced physical activity (PA)
and muscular decits that can limit the autonomous accomplishment of
activities of daily living (ADLs). Increased muscle strength and regular PA
are related to cope with ADLs and thus can provide the greatest possible
autonomy during treatment. However, eects of strengthening exercises
on ADL accomplishment have not yet been examined.
Methods: In this bicentric RCT, we recruited patients (4-18 years) diag-
nosed with acute leukemia or NHL. e control group (CG) was provided
a standard care sports program. e Intervention group (IG) received
standard care combined with a specic strength training. For both groups,
exercise interventions were scheduled 2-3 days per week. At four measure-
ment points, we assessed physical function limitations using the Activities
Scale for Kids© (ASK), exercise-related ADLs with the Functional ADL
Screen, PA level using an accelerometer and motor performance with the
MOON-test.
Results: Over a span of 34 months, we included 41 participants (10.0±4.0
years; 66% male; IG n=21) 15.1±10.2 days post-diagnosis. During the
mean intervention period of 7.4±2.4 months, participants completed
37±21 training sessions, with 29.7±4.7 min on average. Both groups
scored similar cross-sectional and longitudinally increased ASK scores
(IG: 64.6±19.2à85.4±24.3; CG: 68.1±20à86±12.2). Motor performance
was reduced in nearly all abilities compared to reference values. At nal
assessment, IG showed slightly improved motor abilities compared to CG.
Discussion: Functional limitations regarding the ADLs are indicated early
aer diagnosis. Instructed training interventions during acute treatment
support the patients mobility. IG participants show remarkable compli-
ance with strength training.
Conclusion: Our results illustrate that pediatric cancer patients need
access to structured, holistic exercise programs to maintain physical per-
formance, autonomy and activity level over the period of acute treatment.
Disclosure Statement: e authors declare no conict of interest.
791
Evaluation of the eects of a 6-months telemedicine based
exercise intervention on cardiorespiratory tness and quality
of life in cancer survivors
Verena Krell1; Johanna Porst1; Franziska Greiß1; Bernd Wolfarth1
1Charité Universitätsmedizin Berlin, Abteilung Sportmedizin, Berlin,
Deutschland
Background: ere is strong evidence of the benecial eects of physical
activity on physical performance and quality of life in cancer survivors.
Yet, the usual care regarding exercise therapy aer cancer diagnosis is
lacking especially in sparsely populated regions. e aim of this study is
to evaluate the eects of a telemedicine based exercise intervention on
cardiorespiratory tness and quality of life.
Methods: e study is designed for cancer survivors (CS) who have
completed their acute cancer therapy. Based on spiroergometry patients
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts238
of the intervention group (IG) receive an individual training plan with
overall goal of at least 150 minutes physical activity per week. Training
adherence is telemedically recorded and supervised through an activity
tracker. Patients of the control group (CG) receive group exercise therapy
for CS. Primary endpoint is cardiorespiratory tness (VO2peak) measured
at three time points (V0: baseline; V1: aer 6 months intervention; V2:
Follow up aer 12 months). Secondary endpoint is quality of life (QoL)
assessed by questionnaire EORTC QLQ-C30.
Result: Mean relative VO2peak was 25,8±7,1 ml/min/kg for patients of
IG (n=28) and showed no signicant change from V0 to V1. Despite this
there was a signicant change in relative maximum power (Pmax) from
baseline to V1 (p<0,05). For patients of CG (n=15) mean relative VO2peak
was 18,1±3,6 ml/min/kg. In this group neither relative VO2peak nor rela-
tive Pmax changed signicantly from V0 to V1. In IG QoL scale physical
functioning improved signicantly from V0 to V1 (p<0,05). In CG there
was no signicant change in QoL measured.
Discussion: e preliminary evaluation of the telemedicine based exer-
cise intervention shows no improvement on overall cardiorespiratory t-
ness but on QoL scale physical functioning. is indicates that physical
functioning does not only rely on the assumed improvement of cardiore-
spiratory tness.
Conclusion: In order to compare a telemedicine based exercise interven-
tion with group exercise therapy for CS further analyses with higher num-
ber of cases are required.
Disclosure Statement: e authors declare no conict of interest.
1036
A Novel, Long-Acting G-CSF Fusion Protein without
PEGylation in Women with Breast Cancer Receiving
Myelotoxic Chemotherapy – Results of a Pivotal Randomized,
Controlled Clinical Trial
Hartmut Link1; John Glaspy2; William Daley3; Igor Bondarenko4;
Dean Rutty5; Jianmin Chen3
1Hämatologie Internistische Onkologie, Kaiserslautern, Deutschland
2Ronald Reagan UCLA Medical Center, Los Angeles, USA
3Evive Biotechnology Inc, Bridgewater, USA
4Dnipro State Medical University, Dnipro, Ukraine
5Everest Clinical Research, Markham, Ontario, Kanada
Background: Chemotherapy-induced neutropenia (CIN) is the primary
dose-limiting toxicity in patients (pts) receiving myelotoxic chemother-
apy (CTX). Eemalenograstim alfa (F-627) is a novel, non-pegylated,
recombinant fusion protein containing human G-CSF and an IgG2-Fc
fragment, which is intended to reduce CIN by stimulating neutrophilic
proliferation and activation. e study (NCT03252431) evaluated the e-
cacy and safety of F-627 compared to the pegylated lgrastim (PEG-FIL)
Neulasta®.
Methods: 393 female pts with stage I - III breast cancer receiving 4 cycles
of myelotoxic CTX were randomized to F-627 or PEG-FIL (1:1 ratio) and
received the study drug 24 h s.c. aer the last day of CTX administration.
e primary ecacy endpoint was the duration of Grade 4 CIN (ANC
<0.5 × 10 9/L) during cycle 1 of CTX. For non-inferiority analysis, a mar-
gin of 0.6 days was dened.
Result: F-627 was non-inferior compared to PEG-FIL for the duration
of Grade 4 CIN in cycle 1 with a mean dierence of 0.0 days (95% CI:
-0.1, 0.1) and a mean duration 0.2 days in both study groups. e inci-
dence of grade 4 CIN in CTX cycle 1 was 11.7% in both study groups.
For subsequent CTX cycles, the incidence of grade 4 CIN was generally
lower than in CTX cycle 1, with a lower incidence noted for pts random-
ized to F-627 compared to PEG-FIL. e incidence and mean duration of
IV antibiotic use and hospitalization due to febrile CIN were comparable
between F-627 and PEG-FIL. e mean time to ANC nadir was slightly
longer with F-627 than with PEG-FIL. F-627 was well tolerated, with a
low incidence of serious AEs and AEs leading to discontinuation, com-
parable to PEG-FIL. ere were 3 drug-unrelated deaths during the study
(F-627:1, PEG-FIL:2).
Discussion: F-627 was non-inferior to PEG-FIL in reducing the duration
of severe CIN following CTX. Further, F-627 was well tolerated with an
overall safety prole comparable to that for PEG-FIL.
Conclusion: F-627 is the rst long-acting G-CSF without PEGylation
and constitutes a safe, eective, and easy to use alternative to current CIN
prophylaxis.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
Poster
100
Complementary and alternative medicine (CAM) supplements
in cancer outpatients: analyses of usage and of interaction
risks with cancer treatment
Clemens Wolf1; Tobias Rachow1; Thomas Ernst1; Andreas Hochhaus1;
Bijan Zomorodbakhsch2; Susan Foller3; Matthias Rengsberger4;
Michael Hartmann5; Jutta Huebner1
1Universitätsklinikum Jena, Klinik für Innere Medizin II, Hämatologie und
Internistische Onkologie, Jena, Deutschland
2Onkologische Kooperation Harz, Goslar, Deutschland
3Universitätsklinikum Jena, Klinik für Urologie, Jena, Deutschland
4Universitätsklinikum Jena, Klinik und Poliklinik für Frauenheilkunde und
Fortpanzungsmedizin, Jena, Deutschland
5Universitätsklinikum Jena, Apotheke des Universitätsklinikums, Jena,
Deutschland
Background: e aim of our study was to analyze the use of comple-
mentary and alternative medicine (CAM) supplements, identify possible
predictors, and analyze and compile potential interactions of CAM sup-
plements with conventional cancer therapy.
Methods: We included outpatient cancer patients treated at a German
university hospital in March or April 2020. Information was obtained
from questionnaires and patient records. CAM–drug interactions were
identied based on literature research for each active ingredient of the
supplements consumed by the patients.
Results: 37.4% of a total of 115 patients consumed CAM supplements.
Potential interactions with conventional cancer treatment were identied
in 51.2% of these patients. All types of CAM supplements were revealed
to be a potential source for interactions: vitamins, minerals, food and
plant extracts and other processed CAM substances. Younger age (< 62
years) (p = 0.020, φc = 0.229) and duration of individual cancer history of
more than 1 year (p = 0.006, φc = 0.264) were associated with increased
likelihood of CAM supplement use. A wide range of dierent CAM sup-
plement interactions were reviewed: eects of antioxidants, cytochrome
(CYP) interactions, and specic agonistic or antagonistic eects with can-
cer treatment.
Discussion: e interaction risks of conventional cancer therapy with
over-the-counter CAM supplements seem to be underestimated.
Conclusion: Supplements without medical indication, as well as over-
doses, should be avoided, especially in cancer patients. To increase patient
safety, physicians should address the risks of interactions in physician–
patient communication, document the use of CAM supplements in
patient records, and check for interactions.
Indication of source: Wolf CPJG et al., Complementary and alternative
medicine (CAM) supplements in cancer outpatients: analyses of usage
and of interaction risks with cancer treatment. J Cancer Res Clin Oncol.
2021 Jul 6. doi: 10.1007/s00432-021-03675-7
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 239
136
Perceived exertion of sensorimotor training in childhood
cancer survivors
Sarah Otten1; Clémentine Bischo2; Aram Prokop3,4,5; Volker Maas3;
Wilhelm Bloch1; Fiona Streckmann2,6; Julia Däggelmann1;
Vanessa Oschwald1
1Institute of Cardiovascular Research and Sports Medicine, German Sport
University Cologne, Department of Molecular and Cellular Sports Medicine,
Cologne, Deutschland
2Department of Sport, Exercise and Health, University of Basel, Basel, Schweiz
3Childrens Hospital Amsterdamer Straße, Cologne, Clinic for Children and Youth
Medicine, Municipal Clinics of Cologne, Department for pediatric hematology/
oncology, Cologne, Deutschland
4Clinic for Children and Youth Medicine, Helios Clinics of Schwerin, Pediatric
Oncology/Hematology, Schwerin, Deutschland
5Medical School Hamburg (MSH), University of Applied Sciences and Medical
University, Hamburg, Deutschland
6Department of Oncology, University Hospital Basel, Basel, Schweiz
Background: To determine the perceived exertion of sensorimotor train-
ing (SMT) in childhood cancer survivors.
Methods: 6 childhood cancer survivors (mixed diagnoses, 7-15 years)
participated in a 4-week SMT intervention. Training was performed 3x/
week (1x supervised, 2x home-based) and consisted of 5 sensorimotor
exercises (5 reps à 10s with 20s rest, 1min rest between exercises). Exercise
intensity was set by combining various positions, surfaces and dual tasks
resulting in overall exercise intensity levels from 3 (low) to 12 (high).
Perceived exertion was determined (1) per RPE-scale (6-20) aer each
training session and (2) per 5-point-likert scale aer the intervention.
Result: Participants mostly chose the overall exercise intensity levels 8 or
9. Mean RPE-value was 11.43 ± 0.91. 2/6 children rated SMT as somewhat
physical demanding and 4/6 chose the answer cannot decide.
Discussion: While most SMT sessions were performed at medium inten-
sity, participants perceived SMT as less intensive. Many children had
diculties in assessing intensity. is may be due to the fact that they
compared their physical exertion during SMT with their experiences of
general strength and endurance exercises. However, in cancer patients
SMT is not applied to promote strength, but primarily to improve for
example balance control and proprioception by inducing neuronal adap-
tion1. us, SMT requires specic training strategies such as short exercise
durations and sucient time for recovery to prevent neuronal fatigue1.
Conclusion: In order to successfully apply SMT in childhood cancer
survivors to achieve improvements in areas such as balance control and
proprioception, children need to be sensitized to SMT, its potential mech-
anisms and especially to its specic training strategies.
Indication of source:
1 Streckmann F, Rittweger J, Bloch W, Baumann FT (2014) Bewegungsempfeh-
lungen bei Chemotherapie-induzierter peripherer Polyneuropathie. Bewe-
gungstherapie und Gesundheitssport 30:179-182
Disclosure Statement: e authors declare no conict of interest.
137
Smoking patterns and motivation to quit in cancer patients:a
cross-sectional study
Frederike Bokemeyer1; Holger Schulz2; Carsten Bokemeyer3,4;
Christiane Bleich2
1Poliklinik und Institut für Medizinische Psychologie, Universitätsklinikum
Hamburg-Eppendorf , Hamburg, Deutschland
2Poliklinik und Institut für Medizinische Psychologie, Universitätsklinikum
Hamburg Eppendorf, Hamburg, Deutschland
3II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie,
Knochenmarktransplantation mit Abteilung für Pneumologie),
Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland
4Zentrum für Onkologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg,
Deutschland
Background: Continuing to smoke aer cancer can negatively inuence
the course of the disease and the outcome of therapy. Evidence from lit-
erature shows that 40% of patients continue to smoke aer diagnosis.
However, there is still a lack of studies on prevalence, smoking patterns
and motivation to change among cancer patients in Germany and only
few successful international smoking cessation programs exist for these
patients to date. erefore, the aims of this study are: Determination of the
prevalence of smoking cancer patients, smoking patterns, cigarette depen-
dency and the "Stage of Change" concerning the Transtheoretical Model
of Change; identifying sociodemographic, medical, and psychological risk
factors; determination of facilitating and inhibiting factors to take up a
cessation program.
Methods: e study will include more than 1000 cancer patients with
an age of at least 18 and independent of the tumor entity and the phase
of treatment. A questionnaire will be handed out in oncology depart-
ments, outpatient clinics and practices in Hamburg, Germany. e used
instruments are EORTC-QLQ C30 for quality of life, distress thermom-
eter, SSUK for social support, FÄR for the motivation to quit smoking,
FTCD for the cigarette dependency, AUDIT-C for alcohol consumption
and self-developed items for capturing knowledge on the consequences
of smoking as well as qualitative questions regarding own experiences in
prior smoking cessation attempts and needs for future attempts.
Result: Currently more than 846 patients have been recruited. An interim
analysis will be presented.
Discussion: is study is important as there is no comprehensive smok-
ing cessation program for cancer patients in Germany to date. If risk fac-
tors, smoking patterns and motivational aspects of cancer patients are
identied, it is possible to customize smoking cessation programs.
Conclusion: Data on prevalence, smoking behavior, motivational aspects
and potential risk factors will provide a basis for the development of a can-
cer-specic smoking cessation program for German oncological hospitals.
Disclosure Statement: e authors declare no conict of interest.
159
Studydesign of a telemedical training intervention as part
of the study ‘Survivorship Clinic for long-term survivors with
gynecological cancer’
Johanna Porst1; Hannah Woopen2; Jalid Sehouli2; Verena Krell1;
Franziska Greiß1; Stephanie Roll3; Thomas Reinhold3; Stefan N. Willich3;
Maren Keller4; Seyma Boz4; Petra Hühnchen5; Wolfgang Böhmerle5;
Matthias Endres5; Kirsten Wittke6; Carmen Scheibenbogen6;
Adak Pirmorady7; Matthias Rose7; Elisabeth Steinhagen-Thiessen8;
Knut Mai8; Lukas Maurer8; Frank Edelmann9; Reinhold Kreutz10;
Engi Algharably10; Cindy Stoklossa11; Bernd Wolfarth1
1Charité − Universitätsmedizin Berlin, Abteilung für Sportmedizin, Berlin,
Deutschland
2Charité − Universitätsmedizin Berlin, Klinik für Gynäkologie mit Zentrum für
onkologische Chirurgie, Berlin, Deutschland
3Charité − Universitätsmedizin Berlin, Institut für Sozialmedizin, Epidemiologie
und Gesundheitsökonomie, Berlin, Deutschland
4Nord-Ostdeutsche Gesellschaft für Gynäkologische Onkologie e.V., Berlin,
Deutschland
5Charité − Universitätsmedizin Berlin, Klinik für Neurologie, Berlin, Deutschland
6Charité − Universitätsmedizin Berlin, Institut für Medizinische Immunologie,
Berlin, Deutschland
7Charité − Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt für
Psychosomatik, Berlin, Deutschland
8Charité − Universitätsmedizin Berlin, Medizinische Klinik für Endokrinologie,
Diabetes und Stowechselmedizin, Berlin, Deutschland
9Charité − Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt
Kardiologie, Berlin, Deutschland
10Charité − Universitätsmedizin Berlin, Institut für Klinische Pharmakologie und
Toxikologie, Berlin, Deutschland
11Charité − Universitätsmedizin Berlin, Sozialdienst, Berlin, Deutschland
Background: In the framework of the study ‘Survivorship Clinic for long-
term survivors (LTS) with gynecological cancer’, funded by the German
health care Innovation Fund, one component to promote quality of life
(QoL, primary endpoint) in LTS is the module of sports medicine. A
healthy and active lifestyle can reduce risk factors for cancer recurrence
and therapy-associated long-term side eects. us, physical activity
is essential for tertiary prevention. e goal is to establish an ecient
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts240
training protocol that can be transferred into standard care to promote
physical health for LTS.
Methods: Based on parameters determined by sports medical history and
performance diagnostics, 180 LTS of gynecological cancer receive indi-
vidual training plans over 12 months of intervention. Training protocols
are in accordance with the ACSM exercise guidelines for cancer survivors
(Campbell et al., 2019) and aim for moderate endurance (3x30 min/week)
and strength training (2x/week). Training is telemedically supervised
through an activity tracker, a digital exercise journal and telephone con-
sultation every four weeks. Physical activity is also evaluated every three
months with the IPAQ questionnaire in addition to the activity tracker
evaluation. Every patients baseline performance diagnostics results will
be compared with those aer the intervention.
Result: Results will include parameters such as VO2peak, the ventila-
tory thresholds VT1 and VT2, lactate thresholds (individual anaerobic
and 4mmol-threshold) and exercise session adherence aer 12 month of
intervention.
Discussion: Findings of this intervention will provide better knowledge
about the application of sports medical consulting and training manage-
ment through telemedical interventions and the diculties that might
occur in this cohort.
Conclusion: All ndings shall help to establish a sucient protocol for
LTS in the module of sports medicine, with the goal to establish it in stan-
dard care of LTS in gynecological cancer and therefore contribute to a
multidisciplinary approach of promoting QoL.
Disclosure Statement: e authors declare no conict of interest.
169
The impact of whole-body vibration training on the incidence
and the severity of chemotherapy-induced peripheral
neuropathy in breast cancer patients receiving paclitaxel
therapy
Rebecca Dalferth1; Hannah Hebbel1; Nadine Sallach1; Nicolai Maass1;
Anne Letsch2; Thorsten Schmidt2
1Department of Gynecology and Obstetrics, University Medical Center
Schleswig-Holstein (UKSH), Kiel, Deutschland
2University Cancer Center Schleswig-Holstein (UCCSH), University Medical
Center Schleswig-Holstein (UKSH), Kiel, Deutschland
Background: Breast cancer is the most common cancer in women in
Germany and is generally treated with adjuvant chemotherapy, contain-
ing platinum, taxane or vinca alkaloid. e occurrence of chemothera-
py-induced peripheral neuropathy (CIPN) is a very common side eect
of these cytostatic drugs. CIPN can be therapy limiting due to sensorial,
motor, and vegetative impairments. Treatment delay, dose reduction or
discontinuation of the therapy negatively aects the outcome, as well as
the overall survival rate of the patients. In this study we aim to reduce
therapy-induced side eects by application of a supportive sport and
exercise intervention. Positive results will greatly facilitate a more patient-
centered therapy.
Methods: In this prospective randomized controlled trial, 60 breast can-
cer patients are compared regarding the occurrence of CIPN. During the
period of taxane (paclitaxel) administration, two of three study groups
are receiving a twice weekly, one-hour exercise intervention including
strength training or strength training combined with whole-body vibra-
tion (WBV) training. e third group serves as control and does not
receive any training. At xed intervals the patients’ balance and depth
sensitivity are measured, to examine the eect of the exercise intervention
on CIPN-manifestation.
Result: At this point, the study is still in progress. It shows a good feasi-
bility with 35 of 51 patients having completed the nal testing by now. An
overall evaluation of the results will be completed by the time of the con-
gress. e currently available results already show tendencies that exercise
intervention, and particularly WBV training have benecial eects on the
occurrence and the severity of a CIPN.
Discussion: e study is limited by its small size. Furthermore,
patient-questionnaires could not be double-blinded, eventually leading to
a bias in their evaluation.
Conclusion: By mitigating treatment-limiting side eects of CIPN, phys-
ical activity represents a relevant therapeutical option in gynecologic
oncology during paclitaxel therapy.
Disclosure Statement: e authors declare no conict of interest.
172
The impact of whole body vibration on the incidence
and the severity of chemotherapy-induced fatigue and
quality of life in breast carcinoma patients receiving
paclitaxel therapy
Hannah Hebbel1; Rebecca Dalferth1; Nadine Sallach1; Nicolai Maass1;
Anne Letsch2; Thorsten Schmidt2
1Department of Gynecology and Obstetrics, University Medical Center
Schleswig-Holstein (UKSH), Kiel, Deutschland
2University Cancer Center Schleswig-Holstein (UCCSH), University Medical
Center Schleswig-Holstein (UKSH), Kiel, Deutschland
Background: e aim of this prospective randomized controlled study is
to investigate the eectiveness of whole body vibration (WBV) in improv-
ing chemotherapy induced fatigue (CIF) and the quality of life (QOL) in
women with breast cancer receiving paclitaxel.
Methods: 60 breast cancer patients receiving paclitaxel chemotherapy
are randomized into three study groups: strength training (ST), strength
training and whole body vibration (ST+WBV) and control (C). e ST
group absolve a specic strength training two times a week for one hour
while the ST+WBV group has an additional unit on a vibration platform
with a vibrating dumbbell. e control group receives no supervised
exercise training. Primary endpoints CIF, QOL and strength are tested
before the paclitaxel treatment (t1), 6 (t2), 12 (t3) and 18 (t3) weeks aer
the treatment start. Test instruments are the EORTC QLC BR23, C30,
Fatigue/MFI, handmanometry and the chair rising test.
Result: So far, the study shows a good feasibility with 51 patients included
of which 35 completed the program by now. e patient compliance is
very good and the results currently available show tendencies, that WBV
eects CIF and QOL positively. Final results will be available at the time
by the congress in February 2022.
Discussion: CIF and a poor QOL are common reasons for therapy can-
cellation, delay or reduction. If WBV reduces CIF and improves QOL, it
will also have a positive impact on the therapy outcome of those patients.
e studies limitations are its small size and the non-blinded execution
which represents a potential confounder in the analysis of patient-com-
pleted questionnaires.
Conclusion: e preliminary results imply that WBV training benets
women with breast cancer suering from CIF and improves their QOL
so it could become a relevant therapeutic option in gynecologic oncology
during paclitaxel therapy.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 241
180
Patients’ perceptions of an integrated care model in stem
cell transplantation, facilitated by eHealth: Interim results of
a qualitative study, evaluating the implementation process
regarding implementation outcomes and principles of
medical ethics
Linda Wienands1; Julia Krumme2; Lynn Leppla1,3; Alexandra Teynor4;
Sabine Valenta3; Janette Ribaut3; Elisabeth Veronica Mess4;
Sabina De Geest3,5; László Kovács2
1Medical Center University of Freiburg, Faculty of Medicine, Department of
Medicine I, Freiburg im Breisgau, Deutschland
2University of Applied Sciences, Faculty of Liberal Arts and Sciences, Augsburg,
Deutschland
3University of Basel, Institute of Nursing Science, Department Public Health,
Basel, Schweiz
4University of Applied Sciences, Faculty of Computer Science, Augsburg,
Deutschland
5K.U.Leuven, Academic Centre for Nursing and Midwifery, Department of Public
Health and Primary Care, Leuven, Belgien
Background: An integrated care model (ICM) in allogeneic stem cell
transplantation (alloSCT) aims to foster patients’ self-management by a
human (Care Coordinator (CC), educational sessions) and an eHealth
component (remote monitoring system). However, eects of the latter
are associated with ethical issues. For this purpose, we aimed to 1) eval-
uate the implementation process of the ICM regarding implementation
outcomes and medical ethical principles and 2) recommend ethically ori-
ented renements with view to implementation strategies and agile so-
ware development.
Methods: Within a qualitative evaluation study, we conducted N=12
semi-structured interviews with patients post-alloSCT, who experienced
the ICM. Transcripts were analyzed by nursing scientists and ethicists,
using thematic analysis and the framework method. Round tables with
CCs and soware engineers were held to tailor recommendations.
Result: 1) e irritated life and e individual in health care were overar-
ching themes, which explain ndings by contextual and setting factors:
Patients emphasized the importance of CCs as a steady contact in addition
to changing physicians and perceived educational sessions as appropri-
ate and feasible. Feedback was mixed regarding personal benet through
eHealth, which was linked to the need for security due to remote monitor-
ing, technical experience and social support. Ethical issues such as process
transparency, safety issues related to querying symptoms, and exclusions
based on impairment were noted. 2) Ethical recommendations aimed to
provide alternatives to eHealth and create notication features of submit-
ted health data.
Discussion: ICM is a valuable addition to current care, with the human
component as a core element. eHealth is not benecial per se, and despite
renements, it has to be recognized as an adaptable element aer ethical
considerations.
Conclusion: Combining ethics with implementation science and agile
soware development in the evaluation contributes to a responsible use of
eHealth, gaining ground in supportive cancer care.
Disclosure Statement: e authors declare no conict of interest.
197
The role of structural barriers for physical activity behavior
after the cancer diagnosis
Johanna Depenbusch1,2; Joachim Wiskemann3; Alexander Haussmann1;
Angeliki Tsiouris3,4; Laura Schmidt5; Nadine Ungar5; Monika Sieverding5;
Karen Steindorf1
1Deutsches Krebsforschungszentrum (DKFZ) und Nationales Centrum
für Tumorerkrankungen (NCT) Heidelberg, Abteilung Bewegung,
Präventionsforschung und Krebs, Heidelberg, Deutschland
2Universität Heidelberg, Medizinische Fakultät, Heidelberg, Deutschland
3Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg und
Universitätsklinikum Heidelberg, Abteilung Medizinische Onkologie,
Heidelberg, Deutschland
4Universitätsmedizin der Johannes Gutenberg Universität Mainz, Klinik für
Psychosomatische Medizin und Psychotherapie, Mainz, Deutschland
5Universität Heidelberg, Psychologisches Institut, Heidelberg, Deutschland
Background: Dierent barriers have been shown to prevent cancer
patients from pursuing physical activity (PA) aer the diagnosis, but the
role of structural barriers has not been suciently investigated. e cur-
rent study thus aimed to examine determinants of the perception of struc-
tural barriers and its impact on post-diagnosis PA.
Methods: A total of 1299 breast, prostate and colorectal cancer patients
completed a questionnaire on sociodemographic and medical data, pre-
and post-diagnosis PA and perceived PA impediment by seven structural
barriers. Linear regression analyses were used to identify determinants of
the perception of structural barriers. e association between structural
barriers and insucient post-diagnosis PA was evaluated using logistic
regression analyses for the overall sample and for subsamples divided by
pre-diagnosis PA.
Result: Overall, 40-60% of cancer patients felt impeded by structural barri-
ers regarding a lack of disease-adjusted PA oers and support, particularly
those who were younger, not working, had a higher BMI, lower educa-
tion, co-morbidities and reported lacking PA counseling. Individuals who
indicated stronger impediment by structural barriers were signicantly
more likely to be insuciently active post-diagnosis, specically those
with high pre-diagnosis PA.
Discussion: Structural barriers seem to contribute to insucient PA
among people with cancer. Dierences in the perception of barriers with
regard to patient characteristics are relevant for a more specic targeting
of interventions. e association between structural barriers and post-
diagnosis PA further points out the need for tailored PA programs as well
as patient education and support.
Conclusion: Our results highlight important target points for the devel-
opment and implementation of disease-adjusted interventions that might
help cancer patients to overcome structural barriers and improve PA, e.g.
as established in the network OnkoAktiv1.
1 www.netzwerk-onkoaktiv.de
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts242
229
High need for information regarding physical activity in
patients with myeloproliferative neoplasms - results of a
multicenter questionnaire study (OSHO-#97)
Sabine Felser1; Christina Große-Thie1; Christa Unger1; Philipp Le Coutre2;
Susann Schulze3,4; Lars-Olof Muegge5; Julia Grün1; Christian Junghanß1;
East German Study Group of Hematology and Oncology (Osho)6
1Rostock University Medical Center, Department of Medicine Clinic III,
Hematology, Oncology, Palliative Medicine, Rostock, Deutschland
2Campus Virchow-Klinikum, Charité, Medical Clinic with emphasis on
Hematology and Oncology, Berlin, Deutschland
3Krukenberg Cancer Center Halle (Saale), University Hospital Halle,
Halle (Saale), Deutschland
4Carl-von-Basedow-Klinikum, Department of Medicine Clinic II,
Hematology, Oncology, Palliative Medicine, Merseburg, Deutschland
5Heinrich Braun Klinikum Zwickau, Department of Internal Medicine III,
Zwickau, Deutschland
6Ostdeutsche Studiengruppe Hämatologie und Onkologie e. V.,
Leipzig, Deutschland
Background: Cancer and its treatment oen lead to a decrease in physi-
cal and mental performance. To address this fact special exercise recom-
mendations can be given. ese recommendations are commonly derived
from solid tumor patients (pts) studies. In order to minimize the risk of
exercise induced adverse events, the given recommendations are usually
oriented on the current pts side-eects. Pts with myeloproliferative neo-
plasms (MPN) suer frequently from splenomegaly accompanied by loss
of appetite and weight. Further, these patients are oen anticoagulated due
an increased thrombotic event risk. Specic recommendations addressing
these facts are not available. Aim of the study is to characterize MPN spe-
cic symptoms, side eects and anxiety in order to allow the development
of MPN tailored exercise recommendations. In order to increase pts com-
mitment our study also considers patient specic exercise preferences.
Methods: Ongoing MPN pts one-time multicenter anonymous survey
including: (1) demographic data, (2) disease and treatment data, (3) cur-
rent well-being, symptoms, and side eects, and (4) exercise behavior,
information level and preferences1.
Result: A total of 706 questionnaires were analysed. A high rate of dier-
ent symptoms as moderate to high fatigue (54%) and moderate to severe
bone/muscle pain (39%) were observed. Two hundred and three pts (30%)
had an enlarged spleen and 20% had an increased bleeding tendency with
hemorrhage at the time of the survey. More than 40% of pts feel inade-
quately informed about the importance and benets of physical activity,
and 62% would like more information.
Conclusion: MPN pts have a high demand for information regarding the
importance and eects of physical activity.
Indication of source:
1 DRKS-ID: DRKS00023698
Disclosure Statement: e authors declare the following:
Speaker Honorare von Novartis, BMS, Pzer und Incyte
298
Seminar “Patient Empowerment” as a support for
chemotherapy treated patients with breast cancer and
gynecological malignancies - a pilot project of the LMU
Womens Hospital Munich
Hannah Holländer1; Petra Ortner2; Alexander König1; Nicole Erickson3;
Kerstin Hermelink1; Tom Degenhardt1; Sven Mahner1; Nadia Harbeck1;
Rachel Würstlein1
1Klinikum der Universität München, Klinik und Poliklinik für Frauenheilkunde
und Geburtshilfe, München, Deutschland
2POMME-med GmbH, München, Deutschland
3Klinikum der Universität München, Comprehensive Cancer Center (CCC Munich
LMU), München, Deutschland
Background: Cancer patients may substantially benet from supportive
oers. e seminar "Patient Empowerment" was designed to familiarize
patients and their caregivers with supportive measures focusing on under-
standing of disease, therapy and side eect management.
Methods: e seminar consists of two two-hour parts at intervals of one
month and includes a general introduction with time for questions, talks
and discussions with specialists, supplemented by information materials
on the topics nutrition, exercise, psychooncology and complementary
medicine.
Four seminar groups consisting of patients with breast cancer or gyne-
cological malignancy prior to the start of chemotherapy and, optionally, a
caregiver were formed. e evaluation is based on a self-developed ques-
tionnaire as well as validated questionnaires on disease-related quality of
life (QoL) (EORTC-QLQ-C30, BR23, CX24, OV28), anxiety and depres-
sion symptoms (HADS-D) at four time points: before the seminar, aer 4,
9 and 12 weeks. A control group of comparable patients without seminar
participation was evaluated at baseline and aer 12 weeks.
Result: Between October 2020 and May 2021, 19 patients and 9 compan-
ions participated in the seminar. e control group included 20 patients.
Patients and caregivers were highly satised with the seminar and stated
to recommend it (96,4% agreement on both points).
e QoL deteriorated signicantly in the control group and only
slightly in the intervention group (control: w0=67,6; w12=61,7; interven-
tion: w0=60,8; w12=60,7).
A signicant increase could be found in the reported knowledge about
side eects in the intervention group.
Discussion: e seminar was successful as all participants gave positive
feedback and reported increase in knowledge. ere was also a trend in
improved maintenance of QoL which would need to be conrmed by a
larger number of participants.
Conclusion: e contents of the seminar will be made available virtually
to all patients of the oncological day clinic to supplement the therapy with
supportive oers in the best possible way.
Disclosure Statement: e authors declare no conict of interest.
321
Ecacy of face-to-face behavior change counseling
interventions on physical activity behavior in cancer
survivors – a systematic review and meta-analysis
Corinna Meyer-Schwickerath1,2; Christina Morawietz3; Freerk Baumann4;
Gerhard Huber1; Joachim Wiskemann2
1Institut für Sport und Sportwissenschaft Heidelberg, Universität Heidelberg,
Heidelberg, Deutschland
2Nationales Centrum für Tumorerkrankungen – NCT, Heidelberg, Deutschland
3Institut für Sport und Sportwissenschaft, Universität Duisburg-Essen, Duisburg,
Deutschland
4Klinik für Innere Medizin, Uniklink Köln, Köln, Deutschland
Background: is systematic review and meta-analysis of randomized
controlled trials determines the ecacy of face-to-face behavior change
counseling (BCC) interventions on physical activity (PA) behavior in
adult cancer survivors at least pre-and immediately post-intervention
compared to usual care. Additionally, this review aims to answer the ques-
tion which behavior change techniques (BCTs) are most eective.
Methods: A structured search of the databases Medline, OTseeker, PEDro,
the Cochrane Library, and article reference lists was conducted. All tri-
als were critically appraised for methodological quality using the PEDro
scale. e BCC interventions were coded using the BCT Taxonomy (v1).
Random eect meta-analysis explored between group dierences in
PA behavior post intervention. Standardized mean dierences (SMD)
describe eect sizes.
Result: Fourteen studies were included, 12 eect sizes within 11 trials
were pooled in meta-analysis. e SMD between groups favored the
intervention group with a small eect (SMD 0.22; 95% CI 0.11, 0.33;
p < 0.0001). e BCTs “graded tasks, “self-monitoring of behavior”,
action planning” and “habit reversal” were more frequently coded in
more ecacious interventions.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 243
Discussion: Although small dierences are evident, included trials pre-
sented with a broad variety of study components, and characteristics,
which limits the interpretation of eective components.
e behavior change techniques “Graded tasks, “Action planning”,
“Habit reversal”, and “Credible Source” were used in the trials with a
positive eect, but not in the ineective ones.
Conclusion: BCC interventions are eective in increasing PA behavior in
cancer survivors. Further research is needed providing details of delity
assessment and structuring the intervention description by using a BCT
taxonomy. Health care professionals should consider our results while
awaiting further trial evaluation.
Disclosure Statement: e authors declare no conict of interest.
547
Clinical recommendations for treating Chemotherapy-
Induced Peripheral Neuropathy (CIPN) based on expert
opinions and ndings from a systematic scoping review
Nadja Klafke1; Jasmin Bossert1; Birgit Kröger2; Petra Neuberger3;
Ute Heyder4; Monika Layer5; Marcela Winkler6; Christel Idler6;
Elke Kaschdailewitsch7; Rolf Heine8; Heike John9; Tatjana Zielke9;
Beeke Schmeling9; Sosamma Joy10; Isabelle Mertens10; Claudia Witt11;
Diana Steinmann9; Petra Voiss10; Regina Stolz2
1Abteilung Allgemeinmedizin und Versorgungsforschung , Universitätsklinikum
Heidelberg, Heidelberg, Deutschland
2Institut für Allgemeinmedizin und Interprofessionelle Versorgung,
Universitätsklinikum Tübingen, Tübingen, Deutschland
3Nationales Centrum für Tumorerkrankungen, Universitätsklinikum Heidelberg,
Heidelberg, Deutschland
4Onkologie / Chemo Ambulanz Frauenklinik / Kardiologie / Neurologie,
Städtisches Klinikum Karlsruhe, Karlsruhe, Deutschland
5Zentrum für Integrative Onkologie, Kantonsspital St. Gallen, St. Gallen, Schweiz
6Naturheilkunde und Integrative Medizin, Robert-Bosch-Krankenhaus,
Stuttgart, Deutschland
7Zentrum für Integrative Onkologie, Die Filderklinik, Filderstadt, Deutschland
8Netzwerk anthroposophische Pege in Deutschland, Akademie für
Pegeberufe an der Filderklinik, Filderstadt, Deutschland
9Klinik für Strahlentherapie und Spezielle Onkologie, Medizinische Hochschule
Hannover, Hannover, Deutschland
10Klinik für Naturheilkunde und Integrative Medizin, Integrative Onkologie,
Evang. Kliniken Essen-Mitte, Essen, Deutschland
11Institut für komplementäre und Integrative Medizin, Universitätsspital Zürich,
Zürich, Schweiz
Purpose: CIPN is a frequent burden experienced by cancer patients.
Symptoms of CIPN are dicult to treat the conventional way, and patients
highly demand complementary therapies. e purpose of this study was
to provide evidence-based treatment options for the supportive treatment
of CIPN.
Methods: e research question developed from an expert symposium on
supportive management for neuropathy” in 2018 with participants from
Germany and Switzerland experienced in the eld of integrative oncology,
where a consensus process was conducted for presenting interventions for
CIPN treatment management. e review (registered at PROSPERO 2020,
CRD 42020165851) followed the PRISMA-ScR Checklist and the JBI rec-
ommendations for scoping reviews. e literature search was conducted
in the databases of MEDLINE, Cochrane Central, CINAHL, PsycINFO,
and PEDro. All included studies were assessed with CASP.
Results: In total, 17 naturopathic interventions (13 external applications,
hypothermia/cryotherapy, hydrotherapy, and tactile stimulation) were
consented and recommended by the 16 experts. 72 studies with mainly
good study quality, representing 16 complementary treatment options,
were included in the review. ere is external evidence that manipula-
tive therapies (including massage, reexology, therapeutic touch, rhyth-
mical embrocations), movement and mind-body therapies, acupuncture/
acupressure, TENS/Scambler therapy as well as nutritional therapies are
eective complementary treatment options for CIPN.
Discussion: Applications from classical natural medicine seem to pro-
duce positive eects in complex CIPN symptomatology. Future studies
should pay even more attention to methodologically careful study design.
Conclusions: ere are non-pharmacological treatment options available
for the supportive treatment of CIPN and healthcare professionals need to
be educated about them.
Disclosure Statement: e authors declare no conict of interest.
575
Preliminary experiences of a 6-week bicycle ergometer
training for children and adolescents during hospitalization
for acute cancer therapy: Two case studies
Vivien Lösse1; Meinolf Siepermann1; Vanessa Oschwald2; Volker Maas1;
Wilhelm Bloch2; Julia Däggelmann2
1Childrens Hospital Amsterdamer Straße, Cologne, Clinic for Children and Youth
Medicine, Municipal Clinics of Cologne, Department for pediatric hematology/
oncology, Cologne, Deutschland
2Institute of Cardiovascular Research and Sports Medicine, German Sport
University Cologne, Department of Molecular and Cellular Sports Medicine,
Cologne, Deutschland
Purpose To describe preliminarily experiences of bicycle ergometer train-
ing for children and adolescents during hospitalization for acute cancer
therapy.
Methods A supervised 6-week bicycle ergometer training (3x/week) was
oered to pediatric cancer patients during hospitalization for acute can-
cer treatment. Training protocol comprised continuous cycling for at least
10min (max. 40min) at constant speed (cadence: 60-80rpm); workload
was initially set at 0watt and progressively increased if the patient suc-
ceeded to cycle 10 continuous minutes without interruption. Training
attendance, reasons for non-attendance, training duration and achieved
workload were documented.
Results Patient A (female, 10 years, lymphoma) attended 9/18 sessions.
Reasons for non-attendance were: not hospitalized on the day of training
(8x), medical issues (1x). Training duration ranged from 5-16min. Only
cycling without resistance was possible. Patient B (female, 18 years, lym-
phoma) participated in 9/18 sessions. Reasons for non-attendance were:
not hospitalized on the day of training (5x), medical issues (4x). Training
duration ranged from 10-35min. Workload was increased in one session
up to 25watt.
Discussion Both patients could participate in the intervention. However,
attendance rate was relatively low, as the patients were oen not hospital-
ized on the day of training. If admitted, patients could participate in most
of the oered sessions for at least a few minutes. Workload remained low.
Conclusions Low-intensity bicycle ergometer training seems feasible
during hospitalization for acute pediatric cancer therapy. To improve
attendance and overall exercise time, an individualized and exibly
scheduled training (e.g. even twice per day) needs to be oered. Due to
uctuating patient abilities and low exercise capacity, training should be
supervised.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts244
614
Hurdle race for oncological exercise providers: Barriers and
facilitators for the implementation of oncological exercise
programs in the network OnkoAktiv
Annelie Voland1,2; Annette Lohmann1,2; Maximilian Köppel1,2;
Lena Ansmann3; Joachim Wiskemann1,2
1Nationales Centrum für Tumorerkrankungen – NCT, Heidelberg, Deutschland
2Universitätsklinikum Heidelberg, Heidelberg, Deutschland
3Carl von Ossietzky Universität Oldenburg, Department für
Versorgungsforschung, Abteilung Organisationsbezogene
Versorgungsforschung, Oldenburg, Deutschland
Background: A great body of scientic evidence supports the positive
impact of exercise on cancer patients and survivors. However, oncological
exercise provision in Germany is highly heterogeneous and incomplete
in implementation. e network OnkoAktiv (OA) certies exercise insti-
tutions based on quality indicators and connects them with cancer care
providers to oer high quality oncological exercise programs.
Objective: is work evaluates barriers and facilitators for the implemen-
tation of cancer-specic exercise programs within OA.
Methods: is evaluation is executed in a sequential mixed methods
design. Eight qualitative, semi-structured interviews with leading exercise
therapists were conducted based on the CFIR framework. Aer qualita-
tive analysis, a quantitative, cross-sectional questionnaire was developed
based on qualitative results and literature research. e nal survey will
be send out to all certied OA exercise institutions (n=89) via email in
09/2021.
First results: e qualitative analysis shows facilitators in the inner set-
ting of the interviewed institutions such as existing institutional resources
(n=79), e.g. training equipment, time capacities, qualied sta and reg-
ular team meetings. Further, interviewee showed high personal interest
and intrinsic motivation in exercise oncology (n=26) and they observed
a unique selling point of oncological programs in their regions (n=11). In
the outer setting, cooperation with medical professionals (n=27) as well as
professional marketing (n=35) seem to be highly important for successful
implementation. Barriers are indicated in the outer setting, e.g. lack of
cooperation with oncologists and clinics (n=29) and missing exercise-re-
lated guidance and allocations of patients from practitioners (n=21).
Further, clearing costs with health insurances are describes as incomplete
(n=12).
Expectations: We expect detailed information about barriers and facil-
itators regarding the implementation of oncological exercise programs
within OA. Final results will be presented in 02/2022.
Disclosure Statement: e authors declare no conict of interest.
615
Introduction of digital aftercare in oncology
Ivonne Rudolph1; Bettine Bilsing1
1Waldburg- Zeil Kliniken, Rehabilitationsklinik Bad Salzelmen, Schönebeck,
Deutschland
Background: e time- and location-independent training is an advan-
tage of digital aercare and thus a promising addition to the previous
rehabilitation programs on site. A continuous training aer completion
of the rehabilitation is imperative (1, 2). is can be ensured by the dig-
ital aercare. e Rehabilitation Clinic Bad Salzelmen is carrying out a
pilot study concerning oncological digital aercare from July to December
2021. e aim is to familiarize Mamma-Ca patients in rehabilitation with
the possibilities of digital therapy. ereby an awareness of the advantages
that digital aercare can provide shall be created.
Methods: As part of the pilot study, the technical requirements are
explained to the participants in an information event. Following digital
training units are carried out together. Aer completing the rehabilitation,
the women can start training in digital aercare immediately. Participants
receive the individual training plan online and can talk to their therapist
at any time. e focus of the exercises is strengthening and exibility of
shoulders and arms. e primary study goals are evaluating the acceptance
of digital therapy forms and check the participants compliance regarding
digital aercare. Due to the duration of the pilot study, the nal results, the
discussion and the conclusion will be presented at the DKK 2022
Indication of source
1 Jung, A., Y., Behrens, S., Schmidt, M., oene, K., Obi, N., Hüsing,A.,
Benner, A., Steindorf, K., Chang-Claude, J.: Pre- to postdiagnosis lei-
sure-time physical activity and prognosis in postmenopausal breast
cancer survivors. Breast Cancer Research 2019.
2 Buart, L.M., Galvão, D.A., Brug, J., Chinapaw, M. J. M., Newton,
R.U.: Evidence-based physical activity guidelines for cancer survivors:
current guidelines, knowledge gaps and future research directions.
Cancer Treat Rev .2014 Mar 40 (2):327-40.
Disclosure Statement: e authors declare no conict of interest.
621
A Bavarian health care inventory on supportive cancer care
provision (BEQUEST Study): use case cancer associated
thrombosis (CAT):
Vanessa Kratzer1; Frank Ng2; Rupert Bauersachs3; Roman Gerlach4;
Roland Jucknewitz5; Christoph Kalka6; Robert Klamroth7;
Ulrich Mansmann1; Helmut Ostermann8; Jutta Schimmelpfennig9;
Martin Tauscher4; Mandy Schulz2
1Institut für medizinische Informationsverarbeitung, Biometrie und
Epidemiologie, Medizinische Fakultät, München, Deutschland
2Zentralinstitut für die kassenärztliche Versorgung in der Bundesrepublik
Deutschland, Berlin, Deutschland
3Cardioangiologisches Centrum Bethanien (CCB) Gefäß Centrum, Frankfurt,
Deutschland
4Kassenärztliche Vereinigung Bayerns (KVB), München, Deutschland
5AOK Bayern - Die Gesundheitskasse, Regensburg, Deutschland
6Zentrum für Gefässmedizin, Baden, Schweiz
7Klinik für Innere Medizin – Angiologie und Hämostaseologie, Vivantes Klinikum
im Friedrichshain, Berlin, Deutschland
8LMU Klinikum der Universität München - Campus Großhadern, München,
Deutschland
9Aktionsbündnis Thrombose“ der DGA, DGP, GTH,DGG, Deutschen Gefässliga,
Berlin, Deutschland
Background: To provide the best possible and sustainable health care
for patients (pts) with cancer in Bavaria information on epidemiology,
treatment patterns, patient journeys and outcomes are key. Aim of the
BEQUEST (Bedarfsgerechte und Qualitätsorientierte Versorgung von
Patienten mit Venöser rombose in Bayern) study, is the provision of
aforementioned information by a mixed methods design using dierent
data sources for the use case of CAT pts.
Methods: e present study is based on the Bavarian outpatient claims
data of the panel doctors services according to §295 SGB V to determine
epidemiology, diagnostic and treatment patterns, outcomes and settings.
Inclusion criteria is age > 18years with an active cancer (ICD-10-GM: C.
00-99) diagnosis and an incident DVT (I.80).
Result: In Bavaria 38.390 statutory health insured pts (6% of cancer pts)
suered from an incident DVT between 2016-2018. More than half (55.1
%) live in rural areas. Mean age is 69.7 years (median 72.3), 59 % are
female, average Elixhauser comorbidity index score is 6.4. Main underly-
ing diseases are malignant neoplasms of skin, without specic localization,
of gastrointestinal tract, and of breast. On average, 22.4% pts experience a
disorder of veins e.g. post thrombotic syndrome (I.87), 9.1 % suer from
a pulmonary embolism (I.26) within 15 months aer DVT. In large cities
a heterogeneous group of specialists (Vascular surgery, Angiology etc.) is
involved in patient care compared to sparsely populated districts, where
care is concentrated on general practitioners.
Discussion and Conclusion: e results show a signicant number of pts,
mainly elderly, with CAT. At least every h pt suers from a subsequent
event. For a comprehensive analysis on access to equivalent health care,
BEQUEST will focus in further analyses on outcomes and their correlation
with the involved specialist groups and structural regions. Additionally
the physicians and patient perspective is incorporated by two surveys.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 245
630
Target Groups for Exercise Counseling in Multiple Myeloma
Patients: A Latent Prole Analysis
Rea Kühl1; Maximilian Köppel1; Hartmut Goldschmidt2; Joachim
Wiskemann1
1Nationales Centrum für Tumorerkrankungen – NCT, Medizinische Onkologie,
AG Onkologische Sport- und Bewegungstherapie, Heidelberg, Deutschland
2Department Innere Medizin/Klinik für Hämatologie, Onkologie und
Rheumatologie, Myelomzentrum Heideberg, Heidelberg, Deutschland
Background: e safety and ecacy of exercise for cancer patients all
along the trajectory is supported by a large body of evidence. In order to
ensure maximum eects for the individual patient it is important to take
the symptoms, contraindications and competences of exercise into con-
sideration. is is crucial when dealing with complex patients, like those
with multiple myeloma.
Methods: We conducted a survey including 126 patients with multiple
myeloma and assessed their health related quality of life, symptoms such
as pain and fatigue, and physical activity associated health competence
(PAHCO). e resulting data were analyzed via latent prole analysis
(LPA) to identify homogeneous clusters of patients in regards to their
symptoms and PAHCO, which can be utilized as basis for exercise coun-
seling in a very heterogenous population of myeloma patients.
Result: In both analyses the solution involving four distinct proles
showed the best model t. Furthermore, all proles showed high discrim-
inatory power (> 93% probability of prole aliation given the data).
ese proles can be labeled with patients having high, slightly elevated
and decreased as well as low symptom severity for the rst LPA and
patients with high, moderate, moderate-to-low and very low PAHCO. e
prole validation showed high agreement with our hypothesis.
Discussion: e results show that while a proportion of patients need spe-
cic motivational and educational aspects for their exercise counseling,
others already display a high competence in this regard. A proportion of
patients need a very target-specic approach in exercise therapy to reduce
their symptoms while others benet most from a more generic approach
to maintain their well being.
Conclusion: e identied proles allow a personalized approach for the
eectiveness of exercise counseling for cancer patients and promotes a
more ecient allocation of personnel resources.
Disclosure Statement: e authors declare no conict of interest.
647
Exercise in the context of cardiotoxicity in cancer
patients – current evidence and future directions
Nora Zoth1; Annika Tomanek1; Miriam Götte2,3; Uta Dirksen2,3;
Freerk T. Baumann1
1Uniklinik Köln, Klinik für Innere Medizin I, Onkologische Bewegungsmedizin,
Köln, Deutschland
2Universitätsklinikum Essen, Westdeutsches Tumorzentrum, Klinik für
Kinderheilkunde 3, Essen, Deutschland
3Deutsches Konsortium für Translationale Krebsforschung, Standort Essen,
Deutschland
Background: Cardiovascular diseases are one of the leading causes of
non-cancer-related mortality in cancer survivors. us, the need for pre-
ventive strategies as well as early and sensitive predictors of cardiotoxicity
is rising.
Methods: Publications on the eects of exercise in the prevention of
cancer treatment-induced cardiac damages have been overviewed.
Additionally, data regarding cardiovascular function and cardiological
data were analysed.
Result: Pre-clinical research indicates that exercise might be a promising
strategy to prevent chemotherapy-induced cardiac damages. By the time
only less is known about the eects and molecular mechanisms. In clin-
ical research, exercise did neither lead to a signicant impact on the le
ventricular ejection fraction (LVEF) or le ventricular strain (LV strain)
nor on biomarkers as Troponin and Nt-pro BNP. Positive eects, in con-
trast, have been shown on general risk factors for cardiac sequelae such as
bodyweight, hypertension or cardiorespiratory tness. Current research
suggests that Vo2peak is a promising sensitive method to detect early signs
of heart failure.
Discussion: Reductions in LVEF occur late in the course of myocardial
dysfunction aer cardiac damage has already occurred. Cardiorespiratory
tness (VO2peak) is strongly associated with all-cause mortality and
especially cardiac dysfunction and seems to be a promising tool to detect
cardiac damage.
Conclusion: Although evidence is very limited, exercise seems to have
a great potential regarding cardio-protective mechanisms. In particular,
cardiorespiratory function might be an early and sensitive predictor of
cardiotoxicity. Still, the linkage between exercise and cardiotoxicity in
cancer patients remains ambiguous. erefore, as sites of the National
Center for Tumor Diseases (NCT), the University Hospitals Cologne and
Essen, plan to create a multi-centric and multi-disciplinary research proj-
ect, including observational as well as interventional studies.
Disclosure Statement: e authors declare no conict of interest.
659
Eects of a 4-week online-based dance intervention
for childhood cancer survivors on selected motor abilities
Theresa Walz1; Louisa Jung1; Stefan Balzer2; Volker Maas2;
Vanessa Oschwald1; Wilhelm Bloch1; Julia Däggelmann1
1Institute of Cardiovascular Research and Sports Medicine, German Sport
University Cologne, Department of Molecular and Cellular Sports Medicine,
Cologne, Deutschland
2Childrens Hospital Amsterdamer Straße, Cologne, Clinic for Children and Youth
Medicine, Municipal Clinics of Cologne, Department for pediatric hematology/
oncology, Cologne, Deutschland
Purpose To compare the development of selected motor abilities of
childhood cancer survivors with that of healthy peers during an online-
based dance intervention.
Methods 10 children (overall group, age 7-20) including 6 childhood
cancer survivors (patient group, mixed diagnoses) and 4 healthy children
(comparison group) participated in a 4-week online-based dance inter-
vention. Training (2x/week for 30 min via Zoom) comprised a warm-up,
dance choreographies (main part) and stretching exercises. Static balance
(one-leg stand), lower limb strength (5 times sit-to-stand-test), coordi-
nation under time pressure (sideway jumps) and exibility of the ischi-
ocrural musculature (forward bend) were investigated before and aer the
intervention.
Results Forward bend in the patient group and in the overall group and
sideway jumps in the overall group were signicantly improved. Positive
trends were found for sideway jumps in the patient group and one-leg
stand in the overall group.
Discussion e online-based dance intervention seems to have a positive
impact on the motor abilities of participants, that may be due to charac-
teristics of dancing like e.g. changes of direction and stretching exercises.
Pediatric cancer survivors may especially benet regarding exibility and
coordination. As children with cancer oen suer from restricted motor
abilities caused by medical therapy and associated inactivity1, this might
be a reason for the major improvements in this group.
Conclusions In childhood cancer survivors dancing may be a promising
exercise modality to improve restricted motor abilities that are prerequi-
site for being active. Dancing can even be applied online-based.
References:
1 Söntgerath, R. & Eckert, K. (2015). Impairments of Lower Extremity
Muscle Strength and Balance in Childhood Cancer Patients and Survivors:
A Systematic Review. Pediatric hematology and oncology, 32 (8), 585-612
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts246
673
Movement and Exercise Guideline in Pediatric Oncology – an
AWMF-S2k guideline of the Network ActiveOncoKids
Gabriele Gauß1,2; Sabine Kesting3,4; Oliver Basu2,5; Freerk T. Baumann6;
Joachim Boos7; Ursula Creutzig8; Uta Dirksen2,9; Sarah Döring10;
Katharina Eckert11; Robert Erschig12; Anna-Maria Goebel13; Pablo Hernáiz
Driever13; Ingo Menrath14; Aram Prokop15; Dominik Schneider16;
Jannos Siaplaouras17; Sandra Stössel18; Hannah Stalf19; Arne Streitbürger9;
Andreas Wiener20; Joachim Wiskemann21; Torge Wittke22; Miriam Götte2,5
1Universitätsklinikum Essen, Zentrum für Kinder- und Jugendmedizin,
Kinderheilkunde 3, Essen, Deutschland
2Deutsches Konsortium für Translationale Krebsforschung, Standort Essen,
Deutschland
3Technische Universität München, Fakultät für Sport- und
Gesundheitswissenschaften, Lehrstuhl für Präventive Pädiatrie, München,
Deutschland
4Klinikum Schwabing, Klinik und Poliklinik für Kinder- und Jugendmedizin,
Kinderklinik München Schwabing, München, Deutschland
5Universitätsklinikum Essen, Westdeutsches Tumorzentrum, Kinderheilkunde 3,
Essen, Deutschland
6Uniklinik Köln, Klinik für Innere Medizin I, Köln, Deutschland
7Westfälische Wilhelms-Universität Münster, Münster, Deutschland
8Medizinische Hochschule Hannover, Abteilung für Pädiatrische Hämatologie
und Onkologie, Hannover, Deutschland
9 Universitätsklinikum Essen, Klinik für Tumororthopädie und Sarkomchirurgie,
Essen, Deutschland
10Uniklinikum Münster, Physiotherapie Pädiatrie, Münster, Deutschland
11IST-Hochschule für Management, Düsseldorf, Deutschland
12Rehaklinik Katharinenhöhe, Schönwald, Deutschland
13Charité - Universitätsmedizin Berlin, Pädiatrische Klinik mit Schwerpunkt
Onkologie und Hämatologie, Berlin, Deutschland
14Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Klinik für Kinder-
und Jugendmedizin, Lübeck, Deutschland
15Helios Kliniken Schwerin, Kinder- und Jugendmedizin, Schwerin, Deutschland
16Klinikum Dortmund, Klinik für Kinder- und Jugendmedizin, Dortmund,
Deutschland
17Praxis am Herz-Jesu-Krankenhaus, Kinderkardiologie, Fulda, Deutschland
18Universitätsmedizin Mainz, Zentrum für Kinder- und Jugendmedizin, Mainz,
Deutschland
19Universitätsklinikum Frankfurt am Main, Pädiatrische Onkologie, Hämatologie
und Hämaostaseologie, Frankfurt a.M., Deutschland
20Universitätsklinikum Essen, Westdeutsches Protonenzentrum, Essen,
Deutschland
21Universitätsklinikum Heidelberg, Nationales Centrum für Tumorerkrankungen
(NCT) Heidelberg, Abteilung Medizinische Onkologie, Heidelberg, Deutschland
22Universitätsklinikum Halle (Saale), Krukenberg Krebszentrum Halle, Halle
(Saale), Deutschland
Background: Pediatric cancer leads to reduced exercise participation and
only few patients comply with the national recommendations on physical
activity. is physically inactive behavior increases not only the physical
and psychological adverse eects of therapy, but also the incidence and
extent of sequelae. Currently, there is neither nationwide coverage nor
uniform level of knowledge regarding exercise promotion. e objective
of the guideline is to enable qualied exercise interventions through stan-
dardized procedures in addition to regular physiotherapy.
Methods: is guideline addresses the interdisciplinary treatment team
(pediatric oncologists, tumor orthopedists, neuropediatricians, psycho-
social service, physiotherapists, sports physicians, sports scientists, etc.)
as well as decision-makers in acute hospitals and health insurance. We
followed the requirements of the Association of the Scientic Medical
Societies in Germany (AWMF). Contents were based on practical experi-
ence of experts, patient advocates, and scientic ndings.
Result: e guideline consists of 11 recommendations. Recommendations
1 to 4 declare the relevance of implementing exercise promotion and exer-
cise interventions forming the basis of the guideline. Recommendations
5 to 11 address general framework conditions for implementation, the
design of exercise programs, and options to overcome barriers to move.
Discussion: is guideline summarizes existing structures and evidence
in the context of movement and exercise in pediatric oncology. It takes
into consideration the varying needs and characteristics of children and
adolescents as well as existing national and international experience in
this eld. We identied relevant research gaps regarding targeted exercise
interventions that hampered the development of a S3 guideline.
Conclusion: is guideline provides support in implementing exercise in
pediatric oncology.
Disclosure Statement: e authors declare no conict of interest.
682
Same plant- same indication? Comparing plants used in
Traditional European Medicine and Kampo medicine
Sören Klaus Büntzel1, Maria-Louisa Ritschel1, Judith Büntzel2
1Otto von Guericke Universität Magedeburg, Universitätsklinikum Magdeburg,
Magdeburg, Deutschland
2Georg-August-Universität, Universitätsmedizin Göttingen, Klinik für
Hämatologie und Onkologie, Göttingen, Deutschland
Background: Already Hildegard of Bingen described medical plants like
Alpinia ocinarum, that are part of the traditional Japanese Kampo med-
icine. Deviating from this historically known common feature of TEM
and Kampo medicine, we posed the question how much the ocially
mandated canons of German TEM plants and Kampo plants overlap.
Methods: Medicinal plants ocially mandated by the Bundesministerium
für Arzneimittel und Medizinprodukte (BfArM) and 103 ocial Kampo
formulas were searched. A matrix was generated, showing if a medical
plant was used in a certain formula grouping plants of the same fam-
ily together. VENN diagrams were used to nd common TEM/Kampo
plants. Indications of German and Kampo plants were compared using
primary component analysis and heat-map cluster analysis.
Result: Our research yielded 14 plants that are both used in TEM and
Kampo medicine: Alpinia ocinarum, Citrus x aurantium, Foeniculum
vulgare, Angelica spp., Asparagus spp., Cinnamomum spp., Gentiana
spp., Glycyrrhiza spp., Mentha spp., Panax ginseng, Plantago spp., Rheum
spp., Syzygium aromaticum and Zingiber ocinale. While certain plants
share common indications like Panax gingseng or Foeniculum vulgare,
we observed frapping dierences regarding Mentha spp., Angelica spp. or
Zingiber ocinale in primary component analysis.
Discussion: As Kampo medicine garners more and more interest in
Western Europe, we need to assess what dierences and common features
these two traditional medical systems share. We are the rst to compare
medical plants ocially mandated by the BfArM with plants used in 103
Kampo formulas, identifying 14 common plants that, however, dier
sometimes in their indications.
Conclusion: TEM and Kampo medicine share common plants, indica-
tions for using these plants vary between medical systems. Western med-
icine oncologists should be aware of these dierences.
Disclosure Statement: e authors declare no conict of interest.
686
“I do not hear you!” – deaf and hard hearing cancer patients
report their communication experiences
Maximilian Keck1; Jan Münstermann1; Jutta Hübner1; Jens Büntzel2
1Universitätsklinikum Jena, Klinik für Hämatologie und internistische Onkologie,
Jena, Deutschland
2Südharz-Klinikum Nordhausen, Klinik für HNO-Erkrankungen, Nordhausen,
Deutschland
Objective: Hard of hearing and deafness have an high impact on com-
munication between cancer patients and their oncologists. What is the
patients perspective on this problem?
Material and Methods: Together with bad hearing patients we developed
a questionnaire combining ve complexes: WHO-5-wellbeing question-
naire (5 items) Abbreviated Prole of Hearing Aid Benet (APHAB) as
established self estimation of hearing function (24 items), patients expe-
riences in direct conservations with their physicians (15 items), patient’s
diculties in talks (9 items), and patients wishs for further support in the
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 247
eld (7 items). According to APHAB scores we analyzed the experiences,
diculties and support wishes as well as life satisfaction of cancer patients.
Results: We included 104 hard hearing cancer survivors (median age 76.5
a, range 32-90). 56/104 (53.8%) had no hearing aid, 43/48 (89.5%) patients
with hearing aid report benet. Despite hearing aids APHAB scores of
>40% were seen in 46/104 patients (less hearing group 1), compared to 51
patients with APHAB scores <40% (better hearing group 2). We registered
signicant dierences in diculties to talk (20.73 +/- 6.00 vs. 14.93 +/-
6.69, p<0.001), need for further support (13.79 +/- 5.27 vs. 11.21 +/- 4.77,
p=0.02), and well being (12.35 +/-5.68 vs. 15.77 +/- 5.97, p=0.01).
Conclusions: Cancer patients with hearing loss are very restricted in their
understanding of given information. As more hearing loss is seen as more
additional support is necessary to get a sucient information and consent.
ats why, oncologists have to identify deaf and hard hearing patients and
should develop specic education tools for these groups.
Disclosure Statement: e authors declare no conict of interest.
720
Interprofessional counselling of cancer patients on
complementary and integrative health care (CIH):
Development and implementation of a training program
Birgit Kröger1; Lioba Lohmüller1; Ali Behzad2; Ursula Boltenhagen3;
JanGriewatz4; Stefanie Joos1; Anna Kaltenbach3; Nadja Klafke5;
Cornelia Mahler3; Barbara Stein6; Regina Stolz1; Jan Valentini1;
Markus Horneber7
11Institute of General Practice and Interprofessional Care, University Hospital
and Faculty of Medicine Tuebingen, Tübingen, Deutschland
2Department of Internal Medicine, Division of Pneumology, Paracelsus Medical
University, Klinikum Nürnberg, Nürnberg, Deutschland
3Department of Nursing Science, University Tübingen, Tuebingen, Deutschland
4Competence Centre for University Teaching in Medicine Baden-Wuerttemberg,
University of Tuebingen, Tübingen, Deutschland
5Institute of General Practice and Health Services Research, University Hospital
of Heidelberg, Heidelberg, Deutschland
6Department of Psychosomatic Medicine and Psychotherapy, Paracelsus
Medical University, Nuernberg, Nürnberg, Deutschland
7Department of Internal Medicine, Division of Pneumology, Paracelsus Medical
University, Nürnberg, Nürnberg, Deutschland
Background: Interprofessional collaboration among health care profes-
sionals is essential in oncology. CCC-Integrative is a study to investigate
the eects of interprofessional counselling on CIH in comprehensive can-
cer centers. Design and implementation of the training program for the
consulting nurses and physicians are reported.
Methods: e development of the program started with the analysis of
interprofessional models, current evidence on consultations on CIH,
situational demands and education standards. It incorporated outcomes
from a clinical trial (CONGO), a collaborative research project on CIH
(KOKON), elements of a training program for interprofessional team
building (TEAMc) and communication training (COMSKIL). e results
formed the didactical framework for the blended learning which con-
sisted of three main components: a web-based learning management sys-
tem (ILIAS) for content and learning materials, video-based face-to-face
expert led group and video-based sessions that facilitated and guided indi-
vidual and cooperative learning on case vignettes with dierent degrees of
complexity. Ongoing formative evaluation by questionnaires was used to
tailor the program to the needs of the participants. An interdisciplinary
task force coordinated all steps of the process.
Results: e 10-month training program consisted of 13 online sessions
with 3-6 hours duration and provided a web-based platform for concom-
itant learning. e training program contained lectures, case studies and
simulations of patient consultations. Eleven nurses and 11 physicians
completed the training.
Discussion: A novel training program for interprofessional counselling
on CIH was developed and successfully implemented. Further results and
implications will be presented and discussed.
Conclusion: e project could be used as a basis for a sustainable devel-
opment of interprofessional education on CIH for comprehensive cancer
centers.
Disclosure Statement: e authors declare no conict of interest.
725
Supporting patients during the trajectory of immunotherapy
– A qualitative study
Stefanie Mentrup1; Anne Letsch2; Anne Christin Rahn1
1University of Lübeck, Institute for Social Medicine and Epidemiology, Nursing
Research Unit, Lübeck, Deutschland
2University Hospital Schleswig-Holstein, Campus Kiel, Department of
Hematology and Oncology, Kiel, Deutschland
Background: Cancer patients undergoing immunotherapy need to be
accompanied and supported over the whole trajectory of the therapy.
Here, monitoring and identifying immune-related adverse events (irAE)
are important aspects to support the safety and management of cancer
patients. is qualitative study aims to explore how cancer patients under-
going immunotherapy are supported by healthcare professionals (HCPs)
and the challenges in clinical practice.
Methods: Semi-structured interviews were conducted with HCPs who
are in charge of patients treated with immunotherapy and with patient
representatives. Data collection and thematic analysis will be completed
by November 2021.
Result: Twelve interviews were already conducted with 6 nurses, 4 phy-
sicians and 2 patient representatives. Preliminary results indicate that
HCPs oen experience patients with planned immunotherapy adopting
a passive role in making decisions about the treatment. HCPs report to
provide information about immunotherapy and irAE stepwise to patients
and repeating them along the whole course of the treatment. e main
focus of the information about irAE aims to support patients’ self-man-
agement skills in monitoring symptoms. Side eects of the therapy are
regularly monitored in cancer patients. Some clinics have developed their
own checklists for this purpose. Most of the cancer patients seem to be
under pressure in continuing immunotherapy even if they experience
symptoms. erefore, one challenging situation in clinical practice is the
disruption or discontinuation of the therapy. HCPs try to give emotional
support in this situation although the daily throughput of patients in out-
patient clinics is high, and time is oen limited.
Discussion: e support of people undergoing immunotherapy is more
complex than the support in most standard care settings. HCPs must be
well trained and specialized on the specic needs of these patients.
Conclusion: More research is needed to design and evaluate a tailored
support program for patients with immunotherapy to provide holistic,
patient-centered care.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
727
The inuence of a combined vibration and sensomotoric
training on chemotherapy/ immunotherapy induced
polyneuropathy in the upper extremity – rst results
Stefanie Siebert; Jane Kersten; Sarina Kray1; Sarah Man;
Freerk T. Baumann
Uniklinik Köln - CIO, Med 1 - OTT, Köln, Deutschland
Background: Neurotoxic chemotherapy oen leads to peripheral poly-
neuropathies (PNP). Symptoms such as pain, tingling or numbness
restrict the patients’ quality of life. Previous studies show that sensorim-
otor and/or vibration training can have a positive eect on the symptoms
of the lower extremities. Whether preventive treatment with sensorimo-
tor and/or vibration training of patients receiving neurotoxic cytostatics
already inuences the PNP development of the upper extremities has not
yet been investigated.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts248
Method: During a 12-week training intervention, the subjects perform
two training sessions (T) of 60 minutes per week. At the beginning of
the intervention PNP symptoms must not have occurred. e subjects
are randomized into an intervention group and an active control group.
e IG conducts a sensorimotor and vibration training, while the CG
conducts a strength and endurance training. Before and aer the entire
intervention, ne motor skills are collected with the 20 cents test. EORTC-
QLQ-C30 (quality of life), Fact/GOG-Ntx (PNP symptoms) and VAS
(pain) are measured at T8 and T16 in addition to PRE and POST.
Results: e rst data collected do not yet show any trends. More precise
ndings can only be made aer the end of the survey period and the sta-
tistical evaluation.
Discussion: So far, positive changes to chemotherapy-induced PNP were
primarily shown in the lower extremities. erefore, positive tendencies
are expected in the upper extremities, too. To show the need and the fea-
sibility of reducing symptoms of PNP in the upper extremity the pilot
study is initiated. Vibration and sensorimotor training can be a suitable
treatment option. Aer evaluation of the results, a possible causality can
be determined.
Conclusion: e aim of this study is to demonstrate the preventive eects
of sensorimotor and vibration training on the symptoms of chemothera-
py-induced PNP of the upper extremities. Furthermore, the eects of the
intervention on quality of life, pain and functionality are explored.
Disclosure Statement: e authors declare no conict of interest.
735
Inuence of exercise behavior on fatigue syndrome (CRF)
and endurance capacity in cancer survivors – FatiGO-Study
Stefanie Siebert1; Jannike Salchow2; Melina Straub1; David Kroiher1;
Moritz Hahn1; Carrie-Ann Minto2; Marianne Sinn2; Anne Kollikowski3;
Claudia Loeer3; Freerk T. Baumann1
1CIO - Centrum für Integrierte Onkologie Uniklinik Köln, Med 1 - OTT, Köln,
Deutschland
2Universitätsklinikum Hamburg-Eppendorf, Hubertus Wald Tumorzentum,
Universitäres Cancer Center Hamburg , Hamburg, Deutschland
3Universitätsklinikum Würzburg (UKW), Comprehensive Cancer Center (CCC)
Mainfranken, Würzburg, Deutschland
Background: e number of cancer survivors is steadily increasing.
Many still suer from side eects caused by the disease or the therapy.
Cancer- related Fatigue (CRF) is the most common side eect. Supervised
interventions seem to be the best way to ght CRF. Yet, cancer survivors
do not exercise enough and rarely meet general recommendations. ey
also show lower endurance capacity compared to healthy individuals. e
extent to which objectively measured physical activity behavior inuences
CRF and whether higher endurance capacity can improve the eects of
CRF are still largely unclear.
Methods: 15 cancer survivors with CRF who were at least 1 year up to 10
years post-therapy and had at least a fatigue score of ≥ 4 on the numerical
analog scale (NRS) participated in a 4-week multimodal exercise inter-
vention. Study participants were randomly assigned to 4 training groups
that included moderate- or high-intensity strength or endurance training,
and a control group. CRF was assessed pre (t0) and post (t1) interven-
tion using the EORTC QLQ- FA12 (FA12) questionnaire and was self-re-
ported by participants using NRS 3 times daily. Physical activity behavior
(MVPA) was assessed by accelerometer over 7 days during the interven-
tion and endurance capacity (VO2max) was assessed by spiroergometry
at t0 and t1.
Results: e FA12 showed signicant improvement for all subscales and
the Global Fatigue Score with p ≤ .5. e VO2max showed no signicant
improvement from t0 to t1. No correlations were found between FA12 and
VO2max, FA12 and MVPA, and MVPA and NRS. In contrast, a highly
signicant correlation was found for VO2max t0, t1 and MVPA with
p< .001.
Conclusion: Exercise intervention was safe to perform for patients aer
completing cancer treatment with CRF (NRS ≥ 4). Both aerobic and resis-
tance exercise at high and moderate intensity were eective to improve
CRF and great exercise behavior has benecial eects on endurance
performance. Going further, there is evidence that increased endurance
capacity positively aects CRF.
Disclosure Statement: e authors declare no conict of interest.
741
Module preferences and compliance in dierent exercise
modules for young adults with cancer – YOUEX study
Annelie Voland1,2; Timo Niels3; Inaam El-Rajab1,2; Verena Krell4;
Miriam Götte5; Maximilian Köppel1,2; Joachim Wiskemann1,2
1Nationales Centrum für Tumorerkrankungen – NCT, Heidelberg, Deutschland
2Universitätsklinikum Heidelberg, Heidelberg, Deutschland
3Uniklinik Köln, Centrum für Integrierte Onkologie (CIO) Köln, Köln, Deutschland
4Charité - Universitätsmedizin Berlin, Abteilung Sportmedizin, Berlin,
Deutschland
5Universitätsmedizin Essen, Zentrum für Kinder- und Jugendmedizin, Essen,
Deutschland
Background: To date, strong evidence supports the persuasive positive
eects of exercise on cancer treatment-related side eects. Dierent
approaches of oncological exercise programs have been established,
however, the special interests of younger adults with cancer, including
the integration of online-tools, have rarely been considered in exercise
interventions.
Objective: e aim of this study is to analyze three dierent exercise mod-
ules on module preferences and compliance data.
Methods: is 12-week (w) exercise intervention included young adults
with cancer aged 18–39 years who currently have or had a cancer diagno-
sis within the past 5 years. Participants may choose between three exercise
modules (M1: group-based, social media exercise program once a week,
M2: individual home-based training with an online- training app at least
once per week, M3: participation in an in-person exercise program close
to place of residence). e selected module could be replaced or amended
by another module aer 6w (T1).
Results: From n=92 participants who started at T0, 37.0% patients chose
M1, 54.3% M2 and 8.7% M3. 87% (n=80) of patients could be analyzed
at the T1 timepoint (6w) and 80.4% (n=74) at the T2 timepoint (12w).
Dropout rate from T0-T2 was 19.6% (n=18). Patients who only partici-
pated in M1 the whole 12w duration had an overall exercise compliance
of 47,1%. Further, 77,1% of participants who only participated in M2 for
12w, made usage of our training app on average 1x/w. ere are no adher-
ence results for M3. At T1 42.5% (n=34) of patients switched (n=23) or
amended (n=11) their initial module with another aer 6w.
Discussion: Regarding the initial module choice, patients preferred indi-
vidual app-based exercise programs compared to xed group-based exer-
cise sessions. 12w compliance-rate was higher in M2 compared to M1.
Less than half of the participants changed their module aer 6w.
Conclusion: Individual home-based exercise programs seem to be more
attractive and suitable to the special needs of young adults with cancer
than timed once per week online-exercise sessions.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 249
753
Treatment-related side eects, perceived barriers and
knowledge regarding exercise in patients receiving
immunotherapy: A cross-sectional online survey
Nils Scharath1; Philipp Zimmer2; Elke Jäger3; Katharina Graf1
1Institut für onkologische Sport- und Bewegungstherapie, UCT Frankfurt,
Krankenhaus Nordwest, Frankfurt, Deutschland
2Institut für Sport und Sportwissenschaft, TU Dortmund, Dortmund,
Deutschland
3Klinik für Onkologie und Hämatologie, Krankenhaus Nordwest, Frankfurt,
Deutschland
Background: Although extensive evidence underlines the potential of
exercise as a supportive strategy in oncology, the availability of specic
counselling and exercise programs varies considerably between treatment
regimens and phases. Especially for patients with novel anticancer thera-
pies, information about exercise-related aspects such as exercise knowl-
edge, program availability and barriers are missing. us, this survey
examines treatment-related side eects as well as the knowledge and bar-
riers regarding exercise in patients with immunotherapeutic anticancer
treatment.
Methods: An online cross-sectional survey, partly consisting of standard-
ized and validated questionnaires, was conducted via the distribution of
social media (cancer survivor groups) over the timescale of three months.
Results: Up to date 55 participants (m=14, f=41; (51±12,8y) with ongoing
(n=39) or nished (n=16) immunotherapy completed the survey. More
than 60% of the participants experienced cancer-/therapy-related side
eects such as pain (63%), dermatological problems (65%), fatigue (61%),
polyneuropathy (73%), and cognitive impairments (62%) for at least 3x/
week. Perceived barriers to exercise were mainly fatigue (49%), that exer-
cise is not a routine (40%), no tting exercise program (30%), and reduced
physical function (35%). 84% of the patients with ongoing immunother-
apy stated that they were not or poorly informed about exercise as a sup-
portive strategy.
Discussion: e results indicate that patients undergoing immunother-
apy encounter various side eects, that might be mitigated via individually
tailored exercise. Simultaneously, the patients perceive dierent barriers
to exercise and are insuciently informed regarding exercise benets
during their oncological care.
Conclusion: Information and advising strategies targeted to the needs of
patients undergoing immunotherapy seem to be necessary to improve the
knowledge about exercise, to reduce barriers and thus to promote physical
activity and participation in regular exercise routines.
Disclosure Statement: e authors declare no conict of interest.
772
Exercise therapy with multiple myeloma patients: Evaluation
of an oncologic care structure on feasibility, adherence, and
ecacy
Freerk T. Baumann; Michael Mendes Wefelnberg
Universitätsklinikum Köln, Klinik 1 für Innere Medizin, Centrum für Integrierte
Onkologie (CIO) Köln Bonn, Köln, Deutschland
Background: Multiple myeloma (MM) is a severe haemato-oncological
disease with high mortality and increasing incidence rate. Since evidence
on exercise therapy with MM patients remains quite limited, this study
examines real-life data of an oncologic care structure regarding feasibility,
adherence, and ecacy.
Methods: A prospective data evaluation of MM patients who participated
in the oncologic training and exercise therapy (OTT) at the Cologne
University Hospital between 2012 and 2019 was conducted. e data was
successively reduced to four cohorts, intention-to-treat (ITTC), safety
(SC), adherence (AC) and ecacy (EC) and then, evaluated descriptively,
by means of correlation analysis as well as group and time comparisons.
Result: e SC (N = 26) attended exercise therapy on average about one
session per week over a period of eight month. Roughly one third dropped-
out within three months. In the AC (N = 15) BMI at baseline exhibited a
strong and very signicant negative correlation with exercise adherence.
In the EC (N = 8) a signicant improvement in physical functioning and a
tendency towards signicance in fatigue reduction between two MPs at a
median distance of 20 sessions (range: 16 -30) were observed. No adverse
events were documented.
Discussion: Attending MM patients demonstrated feasibility of exercise
therapy. Yet, due to data insuciencies, impact of severe symptoms (e.g.,
bone lesions) as well as mortality on drop-out rates and relatively low
exercise frequency remains speculative. e ndings are generally limited
by the applied reduction process, the post hoc specication of evaluation
methods and unknown circumstances of patients’ admission to OTT.
Conclusion: Exercise interventions for MM patients at the OTT are safe
and feasible. Associations between BMI and exercise adherence as well
improvements in physical functioning and fatigue provide indications for
future conrmatory study designs.
Disclosure Statement: e authors declare no conict of interest.
778
Hygienic concept for oncology exercise therapy treatment
(OTT) with cancer patients during COVID-19 pandemic at the
University Hospital Cologne
Constanze Handmann; Freerk Baumann
Uniklinik Köln, Köln, Deutschland
Background: During the pandemic of COVID-19 most hospitals sig-
nicantly reduced non-emergency admissions and services due to the
increased risk of viral infection. As a result, the recommended self-iso-
lation for cancer patients during pandemic may lead to physical inactiv-
ity and prolonged sitting time. In addition to the negative side eects of
treatment, this lack of physical activity and exertion has further negative
implications for their health, such as decrease in physical performance
and health related quality of life.
Methods: To address this problem the OTT (Onkologische Trainings-und
Bewegungstherapie) of the University Hospital Cologne located in the
Center for Integrated Oncology (CIO) implemented a Hygienic Concept
to ensure safe training session with the physical therapists during COVID
-19 pandemic situation
Result: e need of physical exercise for cancer patients on the one hand,
and protection against the spread of coronavirus on the other hand, infec-
tion control had to be given priority. Although the hygienic concept was
used in the time between September 2020 till August 2021, also during
lock down situation in Cologne. 260 oncologic patients have taken part
in the oncologic exercise therapy. None of the training patients infected
himself with coronavirus during that time period.
Discussion: e hygienic concept was proven safe. Taking into account
the current infection situation and the above-mentioned objectives, the
resumption of regular exercise therapy for cancer patients is necessary but
must take place in another Hygienic Concept compared to non-pandemic
situations.
Conclusion: It should be noted that essential hygiene and infection pro-
tection measures must continue to be observed by all persons involved
in the clinical setting. In addition, it is important to recognize emerging
chains of infection at an early stage and to prevent their spread. It is safe
for cancer patients to use exercise therapy during pandemic situations
when used adapted hygienic concepts.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts250
826
Comparative evaluation of subjectively reported and
objectively measured physical activity in young adults after
childhood, adolescent or young adult cancer within the CARE
for CAYA study
Simon Elmers1; Stanislaus Gröhnke1; Carrie-Ann Minto1; Alexander Stein1;
Jannike Salchow1
1Universitätsklinikum Hamburg-Eppendorf, Universitäres Cancer Center
Hamburg (UCCH), Hamburg, Deutschland
Background: Due to multimodal therapy, the survival rate for cancer in
children, adolescents and young adults (CAYA) has increased. e higher
number of survivors leads to a higher number of late and long-term eects.
Aproximatelly two-thirds of AYAs report therapy-related long-term side
eects. Physical activity (PA) is a well-established method to reduce these
side eects. erefore, it is important to know about the PA behaviour of
cancer survivors. In order to provide insight, various objective and sub-
jective methods of recording PA within the CARE for CAYA study were
compared, with the goal of determining which was the most valid.
Methods: Subjectively reported moderate-to-vigorous PA (MVPA) was
recorded by a physical activity diary (BWT), the CARE for CAYA screening
questionnaire (SF-CfC), and physical activity questionnaire (BSA). Data
was compared with objective measures (MVPA-time, steps), as collected
by the ActiGraph wGT3x-BT. Participants were divided into a suciently
active (≥12,500 steps/day) or insuciently active (<12,500 steps/day)
group. To detect a lack of PA, subjective methods were compared (i.e.
statistically signicant dierences between groups). Receiver Operating
Characteristic (ROC) analysis were used to determine model quality. For
objective measures, motivational and weekend-eects were tested.
Result: 165 CAYAs (mean age 26.5 years, 71.5% female) were included.
SF-CfC (p = 0.489, area-under-the curve (AUC) for ROC analysis: 0.511)
and BSA (p = 0.137, AUC = 0.576) failed to show evidence of signicant
dierences compared to objective measures. BWT (p = 0.001, AUC =
0.682) achieved statistical signicance.
Discussion: Of the compared subjective methods, BWT is the most eec-
tive at identifying a lack of PA. However, it showed weaknesses in deter-
mining PA levels.
Conclusion: With these ndings, it is recommended to continue the use
of both subjective- and objective-measures of PA. Further research should
investigate if there is a motivational eect by wear-ing the ActiGraph and
if there is a dierence in PA levels on weekends.
Disclosure Statement: e authors declare no conict of interest.
874
Feasibility of a Fascia-training in Patients Undergoing
Allogeneic Hematopoietic Cell Transplantation
Sandra Weigmann-Faßbender1,2,3; Hanna Ulbricht1,2,3;
Marianne de Schultz2; Christine Pawandenat1; Desiree Kunadt1,2,3;
Michaela Wol4; Nadine Giesemann2,3,4; Katja Prate1; Johannes
Schetelig1,2,3; Martin Bornhäuser1,2,3; Friedrich Stölzel1,2,3; Nadja Seidel1,2,3;
Friederike Stölzel1,2,3
1University Hospital Carl Gustav Carus Dresden, Dresden, Deutschland
2Medical Faculty Carl Gustav Carus, Technical University Dresden, Dresden,
Deutschland
3National Center for Tumor Diseases Dresden (NCT/UCC), Dresden, Deutschland
4Technical University Dresden, Dresden, Deutschland
Background: Regular Physical Activity (PA) is associated with various
benets for cancer patients. Patients that undergo allogeneic hematopoi-
etic cell transplantation (alloHCT) spend many weeks of treatment in an
isolated environment, oen with little room for exercise. is pilot study
investigated feasibility of a daily performed, unassisted fascia-training and
its eects on back and foot pain, back exibility and quality of life.
Methods: Eighteen alloHCT-patients were randomized to an intervention
(IG: n=9; 60.7± 9.2 years) or control group (CG: n=9; 54.0± 15.5 years)
and assessed from one week before to three weeks aer transplantation
(t0 – t3). CG received standard care physical therapy and IG performed
additionally fascia-training for back and feet twice daily. For both IG and
CG at baseline and three time points aer alloHCT back and foot pain,
back exibility, muscle tone and quality of life were assessed.
Result: Overall, fascia-training was well accepted. No increase in hema-
toma formation was observed. IG reported a trend towards reduction in
back pain from pre- to post-intervention (p = .074), whereas CG showed
a slight increase in back pain at t3 (p = .257). IG also improved back ex-
ibility (-1.79 ± 5.5 cm; p = .397) whereas a decline of back exibility was
observed in CG (+2.71 ± 5.6 cm; p = .167). No dierences between groups
were found for muscle tone. No signicant improvements in quality of life
were reported at t3.
Discussion: is is the rst study investigating feasibility and potential
eects of a special fascia-training in alloHCT-patients. e sample was
small and heterogeneous concerning age, gender and underlying diseases,
but fascia-training was feasible, safe and benecial.
Conclusion: Results of this pilot study suggest that fascia-training has
the potential to improve back exibility, reduce back pain and might be
a valuable component for physical therapy in alloHCT-patients. Further
investigations are necessary to conrm initial ndings of this pilot study.
Disclosure Statement: e authors declare no conict of interest.
951
Interprofessional Communication about Complementary and
Integrative Health (CIH): Development and Implementation of
a Training Program
Ali Behzad1,2; Barbara Stein3; Anna Kaltenbach4; Lioba Lohmüller5;
Birgit Kröger5; Ursula Boltenhagen4; Stefanie Joos5; Nadja Klafke6;
Cornelia Mahler4; Regina Stolz5; Jan Valentini5; Markus Horneber2
1Department of Internal Medicine, University Hospital of Erlangen, Division of
Hematology and Oncology, Erlangen, Deutschland
2Department of Internal Medicine, Paracelsus Medical University, Division of
Pneumology, Nürnberg, Deutschland
3Department of Psychosomatic Medicine, Paracelsus Medical University,
Nürnberg, Deutschland
4Department of Nursing Science, University Tuebingen, Tuebingen,
Deutschland
5Institute of General Practice and Interprofessional Care, University Hospital and
Faculty of Medicine Tuebingen, Tuebingen, Deutschland
6Institute of General Practice and Health Services Research, University Hospital
of Heidelberg, Heidelberg, Deutschland
Background: In the controlled study `CCC-Integrativ´, interprofessional
teams consisting of nurse practitioners and physicians counsel cancer
patients on CIH. e counselling aims to foster patients’ informed deci-
sion making and strengthen self-ecacy. During the study start-up phase,
teams underwent a specialist training on CIH. Here, we report on the
embedded communication skills training (CST).
Methods: Experts in health care communication designed and led
the CST. Design included the following steps: Analysis of challenges
of interprofessional counselling on CIH, adaptation of an existing CST
for medical advice about CIH (COMSKIL-approach developed in the
KOKON-project), its integration into the specialist training on CIH and
adjustment for online training due to the pandemic. Formative evaluation
was used to adapt the training to the participants’ needs.
Results: Based on the theory-founded concept of the COMSKIL pro-
gram, the CST taught core elements of medical communication, specic
elements of interprofessional counselling and motivational interviewing.
It addressed typical situations using case analyses, patient vignettes, role
plays and simulated patients with gradual increase in complexity. e CST
was manualized and 11 nurses and 11 physicians underwent the training.
Discussion: We developed an innovative online CST for nurse practi-
tioners and physicians to foster patient-oriented and motivating counsel-
ling of cancer patients on CIH. e CST was embedded in a specialist
training on CIH, oering the unique opportunity to combine knowledge
transfer and practice of communication skills. It can be used online and
in presence both as a CST in oncology and as an element of an advanced
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 251
training course on CIH. Course, content and evaluation of the CST will
be presented.
Conclusion: Interprofessional counseling on CIH can eectively be
taught online and implemented in advanced training courses.
Disclosure Statement: e authors declare no conict of interest.
974
Feasibility and adherence of a playful sensorimotor training
for children and adolescents during acute cancer therapy
Theresa Kömpel1; Sarah Otten2; Meinolf Siepermann3;
Clémentine Bischo4; Melanie Reitz2; Fiona Streckmann5;
Julia Däggelmann2; Wilhelm Bloch2; Vanessa Oschwald2
1Institut für Kreislauorschung und Sportmedizin, Abteilung Molekulare und
zelluläre Sportmedizin, Köln, Deutschland
2Institut für Kreislauorschung und Sportmedizin, Abteilung Molekulare und
zelluläre Sportmedizin, Am Sportpark Mpngersdorf 6, Köln, Deutschland
3Kliniken der Stadt Köln gGmbH , Kinderkrankenhaus Amsterdamer Straße,
Abteilung für Kinderonkologie und Kinderhämatologie, Köln, Deutschland
4Universität Basel, Deparment für Sport, Bewegung und Gesundheit, Abteilung
Bewegungs- und Trainingswissenschaften, Basel, Schweiz
5Universität Basel, Deparment für Sport, Bewegung und Gesundheit, Abteilung
Bewegungs- und Trainingswissenschaften, Basel, Schweiz
Purpose To determine the feasibility and satisfaction of sensorimotor
training (SMT) which is applied using an age-specic card game during
acute cancer therapy.
Methods A four-week SMT intervention is conducted in pediatric cancer
patients (age 6-21). Training is performed 3x/week (every 2nd supervised)
and consists of 3-6 sensorimotor exercises (5 reps à 20s with 20s rest, 1min
rest between exercises). To respect self-determination during therapy,
patients can individually choose severity level using a specic card game,
which allows them to combine various positions, surfaces and dual tasks.
Feasibility and training satisfaction are assessed using a self-developed
questionnaire aer the intervention.
Results Study recruitment started in March 2022. Preliminary results will
be available and presented at the congress. Positive outcomes are expected
regarding training feasibility and training satisfaction.
Discussion SMT can induce neural adaptations. In pediatric oncology,
SMT is therefore applied to improve sensory and motor dysfunctions that
impact developmental milestones. Initial eects could already be demon-
strated in pediatric cancer survivors. Studies in adults have shown that
SMT is a promising training method1. For children and adolescents during
acute cancer therapy, SMT therefore seems to be a promising training
method, as well. By using a specic card game to set severity level, indi-
vidual adaptations to the patients’ health status and promotion of self-de-
termination are possible. Also, training motivation can be augmented.
Conclusions For children and adolescents during acute cancer therapy,
SMT can be a promising method to maintain or restore crucial bal-
ance skills. In this context, a playful implementation with a card game,
adapted to individual abilities, can promote satisfaction, fun and training
motivation.
References
1 Streckmann F, Balke M, Cavaletti G, Toscanelli A, Bloch W, Décard BF, Leh-
mann HC, Faude O (2021) Exercise and Neuropathy: Systematic Review with
Meta-Analysis. Sports Medicine 52(5): 1043-1065
Disclosure Statement: e authors declare no conict of interest.
987
Perceived eects of a 4-Week-Sensorimotor Training-
Intervention in childhood cancer patients on selected physical
abilities
Melanie Reitz1; Sarah Otten1; Stefan Balzer2; Vivien Lösse2;
Theresa Kömpel1; Julia Däggelmann1; Wilhelm Bloch1; Vanessa Oschwald1
1Deutsche Sporthochschule Köln, Institut für Kreislauorschung und
Sportmedizin, Molekulare und zelluläre Sportmedizin, Köln, Deutschland
2Kinderkrankenhaus Amsterdamer Straße, Köln, Deutschland
Background: To determine the perceived eects of a sensorimotor train-
ing (SMT) on selected physical abilities in childhood cancer patients
receiving acute medical treatment.
Methods: A 4-week SMT-Intervention in childhood cancer patients
receiving acute medical treatment (mixed diagnoses, 5-21 years) is con-
ducted. SMT training is performed 3x/week (each 2nd session is super-
vised). 3-5 exercises/session are performed (5 reps à 20s followed by 20s
rest, 1 min rest between exercises). Participants select the exercise intensity
by combining dierent exercise positions, surfaces and dual tasks using a
specic card-game. Perceived eects are assessed using a self-developed
questionnaire (5-point-likert scale) following the 4-week intervention.
Result: Study recruitment started in March 2022. Preliminary results will
be available and presented at the congress. We expect improvements in
perceived physical abilities.
Discussion: Children with cancer oen suer from physical perfor-
mance limitations, which may impact their mobility and physical activity.
Further, SMT is a form of neuromuscular training to promote balance and
functional performance1. us, it may be a benecial exercise strategy in
pediatric oncology. Perceived and objective eects should be investigated.
Conclusion: SMT may be eective to promote balance and related phys-
ical abilities in children with cancer. SMT may be considered as an addi-
tional exercise therapy strategy.
Indication of source:
1 Streckmann, F., Rittweger, J., Bloch, W., Baumann, F.T. (2014). Bewegungs-
empfehlungen bei Chemotherapie-induzierter peripherer Polyneuropathie.
Bewegungstherapie und Gesundheitssport, 30, 179-182.
Disclosure Statement: e authors declare no conict of interest.
1040
Eects of exercise on chemotherapy-induced peripheral
neuropathy, cancer-related fatigue and sleep quality during
neurotoxic chemotherapy
Jana Müller1; Charlotte Kreutz2; Andreas Schneeweiss3;
Georg Martin Haag4; Karen Steindorf2; Markus Weiler5;
Joachim Wiskemann1
1Heidelberg University Hospital, National Center for Tumor Diseases (NCT)
Heidelberg, Division of Medical Oncology, Working Group Exercise Oncology,
Heidelberg, Deutschland
2German Cancer Research Center (DKFZ), Division of Physical Activity,
Prevention and Cancer, Heidelberg, Deutschland
3Heidelberg University Hospital, National Center for Tumor Diseases (NCT)
Heidelberg, Division of Gynecological Oncology, Heidelberg, Deutschland
4Heidelberg University Hospital, National Center for Tumor Diseases (NCT)
Heidelberg, Division of Medical Oncology, Heidelberg, Deutschland
5Heidelberg University Hospital, Department of Neurology, Heidelberg,
Deutschland
Background: (Neurotoxic) Chemotherapy can have profound negative
eects at the biopsychosocial level. is secondary analysis extends pre-
vious analyses with the aim of comprehensively investigating whether
a sensorimotor- (SMT) and resistance training (RT) may aect subjec-
tively perceived chemotherapy-induced peripheral neuropathy (CIPN)
symptoms [1] as well as fatigue and sleep quality during neurotoxic
chemotherapy.
Methods: 170 patients were randomized to SMT, RT or usual care (UC).
Patients exercised 3×/week (105 min/week) during neurotoxic chemother-
apy (mean length: 20 weeks). CIPN symptoms (EORTC CIPN20), fatigue
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts252
(MFI), and sleep quality (PSQI), were assessed before and 3 weeks aer
neurotoxic chemotherapy. Analysis-of-covariance models were applied
(covariates: age, gender, neurotoxic chemotherapy class, baseline value of
the respective dependent variable, and optional CIPN symptoms).
Result: CIPN symptoms, general, physical, and mental fatigue increased
in all groups (p<.05), while sleep quality remained unchanged. Intention-
to-treat analyses (N=159) revealed no dierences. Exploratory per-pro-
tocol analyses (training attendance rate ≥ 67%; N=89) indicated that
sensory symptoms in the feet, general and physical fatigue and reduced
activity increased less during chemotherapy in the adherent exercisers
(pooled group: SMT+RT) compared to UC (p<.04). Inclusion of CIPN
symptoms as a covariate resulted in non-signicant eects for all fatigue
dimensions except general fatigue.
Discussion: In contrast to other research, sleep quality was not aected
by exercise, probably due to a ceiling eect. Of note, the eects on fatigue
were inuenced by CIPN symptoms, raising the question if the MFI is a
valid questionnaire for detecting fatigue in CIPN patients.
Conclusion: SMT and/or RT may alleviate CIPN symptoms [1]
and probably fatigue in patients undergoing neurotoxic chemotherapy, if
an appropriate training stimulus is achieved.
e authors declare no conict of interest.
Reference:
[1] Müller 2021 BJC https://doi.org/10.1038/s41416-021-01471-1
Disclosure Statement: e authors declare no conict of interest.
Surgical Oncology
Best-of-Abstract-Vortrag
396
Mortality and complication management after surgery for
Esophageal, Gastric, Pancreatic and Liver cancer patients
based on the DKG minimum caseloads
Konstantin Uttinger1; Johannes Diers2; Christoph-Thomas Germer3;
Armin Wiegering3
1Uniklinikum Leipzig, Viszeralchirurgie, Leipzig, Deutschland
2Krankenhaus Havelhöhe Berlin, Innere Medizin, Berlin, Deutschland
3Uniklinikum Würzburg, Chirurgie I, Berlin, Deutschland
Background: e German Cancer Society (DKG) board certies cancer
centers in treating esophageal, gastric, liver and pancreatic cancer among
others. One major criterion used is annual surgical caseload. To this date,
there has been no systematic verication of the number of yearly surgical
resections set by DKG with regards to in-house mortality and failure to
rescue (FtR).
Methods: is is a retrospective analysis of anonymized nationwide hos-
pital billing data (DRG data, 2009-2017). In correspondance with the
Ocial Oce of Statistics in Germany and their data protection guide-
lines, patients were identied using ICD and/or OPS codes as certied
by the DKG.
Results: 171,099 patients were identied based on DKG certication,
including 30,810 Esophageal, 54,155 Gastric, 57,343 Pancreatic and
28,791 Liver resections. Overall in-house mortality ranged between 6.2%
(Gastric resections) and 8.1% (Pancreatic resections). Dierences in
in-house mortality between hospitals which fullled the surgical (annual)
minimum caseload (SMC) and those which did not fulll SMC on average
was 2.9% (5.3% vs 8.2%) in Esophageal, 2.0% (4.8% vs 6.8%) in Gastric
and 3.7% (6.1% vs 9.8%) in Pancreatic cancer patients, while it was -0.6%
(7.6% vs 7.0%) in Liver cancer patients. Complication occurrence rates
for Esophageal, Gastric and Pancreatic resections were similar in hospitals
which did or did not fulll SMC while FtR in hospitals fullling SMC was
signicantly lower in case of occurrence of any complication. In addition,
a statistical model demonstrated that SMC should be risen in esophageal,
gastric and pancreatic resections.
Discussion: In Liver cancer patients, outcome has no clear correlation
with annual surgical volume suggesting that dierent quality indicators
may be of signicance in this patient group.
Conclusion: is study demonstrates an association between fulllment
of SMC set by DKG and lower FtR in Esophageal, Gastric and Pancreatic
cancer patients and improved in-house mortality rate.
Disclosure Statement: e authors declare no conict of interest.
Poster
601
SOCIUS Mentoring - A novel approach to motivate and
prepare students for a career in surgical oncology
Rüdiger Klapdor1; Peter Hillemanns1; Hermann Hertel1; Kai Timrott2;
Florian Imkamp3,4
1Klinik für Frauenheilkunde und Geburtshilfe, Medizinische Hochschule
Hannover, Hannover, Deutschland
2Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Medizinische
Hochschule Hannover, Hannover, Deutschland
3Klinik für Urologie, Vinzenzkrankenhaus Hannover, Hannover, Deutschland
4Klinik für Urologie und urologische Onkologie, Medizinische Hochschule
Hannover, Hannover, Deutschland
Background: e shortage of physicians poses increasing challenges
to surgical disciplines, especially in university medicine. Students lose
interest in surgery during their studies or during their practical year.
To counteract this development, students need to be more strongly and
sustainably inspired. e Surgical Oncology Curriculum for individual
support of ambitious students (SOCIUS) is intended to optimally prepare
students for a career in university surgical oncology.
Methods: As a cooperation between Gynecology, Visceral Surgery and
Urology, a one-year mentoring program for outstanding students was
planned, consisting of six modules and 80 teaching units. Core elements
of the program, in addition to mentoring by clinically and scientically
successful physicians, are the training of operative skills on state-of-the-
art simulators and, in particular, specic so skills that are necessary for
a successful career. Visitations in the participating clinics and congress
participations round o the program. e impact of the program is eval-
uated through the change in participants’ condence and surgical skills
using standardized tests.
Result: In two years, 20 students were selected from 100 excellent appli-
cations. e students signicantly improved their surgical skills and so
skills. is was documented by increased condence scores. In addition,
the students stated that they had specied their career goals and gained
more self-condence in surgery, as well as seeing more potential in a sur-
gical career. Satisfaction with the program is also reected in the absolute
recommendation rate of the course to friends (MW 5.0, scale 1-5).
Conclusion: Individual support of students through a combination of
mentoring and skills training is a promising way to prepare and motivate
students for their residency in surgical disciplines and thus to counteract
the shortage of young talent in surgical disciplines.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 253
604
Peritoneal tumor lesions (PTLs) - spectrum of diagnoses,
surgical interventions and outcome in a representative case
series at a tertiary center
Frederike Weber1; Tatiana Oksentyuk Polyakova1; Christine March2; Kai
Weger3; Roland S. Croner1; Frank Meyer1
1Klinik für Allgemein-, Viszeral-, Gefäß- und Transplantationschirurgie,
Universitätsklinikum Magdeburg A.ö.R., Magdeburg, Deutschland
2Klinik für Radiologie und Nuklearmedizin, Universitätsklinikum Magdeburg
A.ö.R., Magdeburg, Deutschland
3Institut für Pathologie, Universitätsklinikum Magdeburg A.ö.R., Magdeburg,
Deutschland
Aim: Exemplary demonstration of 7 cases with rare PTLs and their
histopathological results in abdominal surgery emphasizing biological
diversity.
Method: Representative selection of scientic case reports
Results:
1) Diverticulum of the jejunum with pancreatic metaplasia: Intraoperative
incidental nding of a jejunal PTL during gynecological surgery of
endometrium carcinoma lead to segmental resection and reconstruc-
tion with side-to-side jejunojejunostomy.
2) Twisted “appendix epiploicae” (with lipobrosis and necrosis of the
appendix): Patient with progressive abdominal pain in the right lower
abdomen was diagnosed with acute appendicitis followed by laparo-
scopic appendectomy with partial resection of the greater omentum.
3) Acute epiploic appendagitis: In laparoscopic hernioplasty of incarcer-
ated trocar hernia, a suspicious inamed fatty tumor-like tissue was
resected from the descending colon.
4) Primary peritoneal cancer: During explorative laparotomy for ovar-
ian tumor, multiple 8- to 15-mm PTLs were found and subsequently
resected along with radical hysterectomy resulting in R0 resection sta-
tus (5 years ago, mastectomy for breast cancer).
5) Primary serous papillary adenocarcinoma of the peritoneum (his-
tological nding): Patient underwent subtotal peritonectomy, right
hemicolectomy, partial resection of the urinary bladder and HIPEC.
6) Pseudomyxoma peritonei: Patient with PTL (PCI: 32) of unknown
origin underwent palliative ileocoecal resection including 4 PTLs of
mucinous adenocarcinoma.
7) Plant food ingredients (plus older fat necrosis mimicking PTL): In a
patient with chronic subileus, small PTLs were found causing scar-
ring adhesion of the jejunum aer previous appendectomy and ileum
resection.
Conclusion: PTL can comprise diverse origins and entities.
Histopathological investigation and close cooperation of the pathologist
and surgeon can be considered a substantial prerequisite (necessary due to
their rareness) for denite diagnosis-nding, following decision-making
and further therapeutic steps using various modi.
Disclosure Statement: e authors declare no conict of interest.
767
Does VO2-peak provide a prognostic value in esophagectomy
and gastrectomy for post-operative outcomes?
Timo Niels1; Christoph Tobias Heinrich Baltin2; Guido Kosanke3; Ulrich
Klaus Fetzner4; Arnulf H Hoelscher5; Elfriede Bollschweiler3; Jan-Hendrik
Naendrup1; Freerk T. Baumann1
1Department I of Internal Medicine, University, Hospital of Cologne,
Deutschland, Center of Integrated Oncology Aachen Bonn Cologne Düsseldorf,
Deutschland
2Department of Orthopaedics and Trauma Surgery, , University Hospital of
Cologne, Cologne, Deutschland
3Medical Faculty University of Cologne, Deutschland
4Department of General Surgery, Visceral-, Pediatric-, Thoracic- & Endocrine
Surgery, Johannes Wesling, University Hospital of Minden, Deutschland
5Contilia Centre for Esophageal Diseases, Elisabeth Hospital Essen, Essen,
Deutschland
Background: Esophagectomy and gastrectomy are procedures with con-
siderable physical burden and intense post-operative care for the patient.
e physical condition seems to be relevant in prediction of the post-op-
erative care. e VO2-peak value provides the gold standard for the
assessment of the physical performance. erefore, this pilot-study exam-
ined the prognostic value of the VO2-peak on post-surgery outcomes in
esophageal and gastric cancer patients.
Methods: In this prospective cross-sectional study, patients scheduled for
esophagectomy or gastrectomy were examined 24h-prior surgery regard-
ing their functional VO2-capacity (VO2-peak). e post-operative com-
plications according to Clavien-Dindo (CD) grade 3b or above, Intensive
Care Unit (ICU-) days and length of hospital stay were documented fol-
lowing surgery.
Result: e functional capacity was signicantly reduced in 34/35
included patients compared to gender-, age and body weight-matched
norm-values. Following surgery, the average hospital stay was 19,6 days,
the mean ICU-stay 5,8 days and patients experienced a mean of 0,46 com-
plications of CD grade 3b/above. No signicant correlations were found
between VO2-peak values and post-operative outcomes. No predictor
power of VO2-peak was observed. A subgroup comparison of patients
with a VO2-peak <17ml/min/kg and =/>17ml/min/kg suggested descrip-
tive dierences in post-surgery outcomes favouring the tter subgroup,
but non-signicantly.
Discussion: We observed heavily reduced physical perfomance capacity
pre-surgery, possibly caused by previous neoadjuvant treatment proce-
dures. e prognostic-value of VO2-peak remains uncertain within this
pilot-study due to noticeable descriptive dierences but no signicant
correlations or predictor power, potentially limited by the small-sized
population.
Conclusion: e impaired functional capacity shown in this pilot-study
may strengthen the rational for exercise programs during neoadjuvant
and pre-surgery phase.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts254
895
Shortening time to diagnosis in malignant spinal lesions using
a novel diagnostic fast track- a multidisciplinary approach
Annika Heuer1,2; Leon-Gordian Koepke2; Martin Stangenberg2;
André Strahl3; Marc Dreimann2; Lutz Welker4; Carsten Bokemeyer5;
Lennart Viezens2; Anne Marie Asemissen5
1Mildred Scheel Cancer Career Center HaTriCS4, University Medical Center
Hamburg-Eppendorf, Hamburg, Deutschland
2Department of Trauma and Orthopedic Surgery, University Medical Center
Hamburg-Eppendorf (UKE), Division of Spine Surgery, Hamburg, Deutschland
3Department of Trauma and Orthopedic Surgery, University Medical Center
Hamburg-Eppendorf (UKE), Division of Orthopedics, Hamburg, Deutschland
4Institute of Pathology with the Sections Molecular Pathology and
Cytopathology, University Medical Center Hamburg-Eppendorf (UKE),
Hamburg, Deutschland
5Hubertus Wald University Cancer Center, University Medical Center Hamburg-
Eppendorf (UKE), Department of Oncology, Hematology and Bone Marrow
Transplantation with Section Pneumology, Hamburg, Deutschland
Background: Up to 20% of patients (pt) with prior unknown malignancy
present initially due to spinal lesions. Histopathological (HP) examination
represents the diagnostic gold standard. However, decalcication of bone
samples takes up to 14 days. Despite its potential for quicker diagnostic
information, intralesional aspiration cytology (IAC) has not been rou-
tinely performed during spine surgery. We introduced supplementary IAC
in 2020 as part of a multidisciplinary approach aiming to shorten time to
diagnosis (TTD). Methods: Pt requiring spine surgical intervention due to
spinal lesions of unknown origin received intraoperative IAC via transpe-
dicular biopsy of the vertebral body. Cytologic specimens were evaluated
using May-Gruenwald-Giemsa stain by a board-certied hemato-oncolo-
gist. HP specimen analyses were performed standardized. Retrospectively
statistical analysis was performed using the student’s t-test and Cohens
kappa.
Result: To date, 50 pt (38% female) with a median age of 48.9 ± 30.1 years
were included. 5 pt showed no evidence of malignancy. Multiple myeloma
and solid neoplasia were diagnosed in 22 and 66 % respectively by HP.
Compared to HP, IAC detected malignant lesions with a sensitivity of
0.97, specicity of 0.80, and diagnostic certainty of 0.9. With respect to
detection of malignant cells and dierentiation between hematologic or
solid neoplasia, concordance between HP and IAC was 0.922 (kappa).
Mean TTD using IAC was 1.8 ± 1.8 d, whereas HP results were received
aer 8.8 ± 3.5 d (p < 0.001). In 13 pts (26%) specic oncologic therapy
was initiated before the nal HP report was available, based on clinical
variables, staging, and IAC.
Discussion: IAC shows high sensitivity, specicity as well as diagnostic
certainty. TTD can be signicantly shortened by IAC which might lead to
improved patients’ guidance as initial diagnosis carries signicant treat-
ment, prognostic and emotional weight.
Conclusion: IAC can be performed safely and should be implemented
routinely in multidisciplinary spine surgical pathways to improve treat-
ment planning.
Disclosure Statement: e authors declare no conict of interest.
Translational Oncology
Poster
104
Perfusion bioreactor to preserve the microenvironment of ex
vivo hepatocellular carcinoma
Gabriel Fridolin Hess1,2; Mairene Coto-Llerena2,3;
Manuele Giuseppe Muraro2; Caner Ercan2,3; Otto Kollmar1;
Salvatore Piscuoglio2,3; Savas Deniz Soysal1
1Clarunis Viszeralchirurgie, Universitätsspital Basel, Basel, Schweiz
2Departement Biomedizin, Universität Basel und Universitätsspital Basel, Basel,
Schweiz
3Pathologie, Universitätsspital Basel, Basel, Schweiz
Purpose: Hepatocellular carcinoma (HCC) represents an attractive target
for immune checkpoint inhibitors (ICI) and tumor microenvironment
(TME) agents. Patient-derived organoids (PDO) have emerged as models
for ex vivo drug testing. However, the lack of TME and of the immune
cells (IC) hamper their use in the evaluation of ICI and TME-agents. Here,
we developed and characterized a bioreactor-cultivated HCC tissue model
that preserves the tumor tissue architecture and maintains the pathophys-
iological microenvironment of human tissue.
Methods: Tumor fragments of 3mm were installed between two discs of
collagen type 1 scaold and placed in a perfusion bioreactor (U-shaped
Culture Under Perfusion; U-CUP). Cell viability and morphology was
monitored on day 1, 5 and 7. At each time point, fragments were forma-
lin-xed and paran-embedded for downstream analysis. e changes in
TME composition were monitored by immunohistochemistry using cell-
type specic antibodies.
Results: Microscopic analysis revealed that the morphology and the via-
bility of the cells were preserved during the culture period in the U-CUP
at each time point. Tissue histology as well as the immunophenotypic
pattern observed in the original tissue for specic markers such as argi-
nase, was maintained. Endothelial cells and broblasts, identied by the
expression of CD31 and a-SMA, were detected in the U-CUP cultured
samples in a similar proportion to the original tumor samples. e pres-
ence of IC, described by the expression of CD3, was detected at all time
points.
Discussion: Patient-derived organoids from HCC have shown to pre-
serve the genetic characteristic of the tumor, however lacking TME and
IC components. Bioreactor technology has been used in the context of tis-
sue regeneration previously. Compared to the PDO, U-CUP has shown to
preserve mesenchymal and immune components in HCC tissue, allowing
the assessment of TME-related treatments.
Conclusions: U-CUP HCC is a promising option for ex-vivo testing ICI
and TME-agents in HCC.
Disclosure Statement: e authors declare no conict of interest.
199
CAF-associated signaling pathways are linked to platinum
resistance in high-grade serous ovarian carcinoma
Michael Wessolly1; Elena Mairinger1; Sabrina Borchert1; Agnes Bankfalvi1;
Pawel Mach2; Kurt Werner Schmid1; Rainer Kimmig2; Paul Burderath2;
Fabian Dominik Mairinger1
1University Hospital Essen, Institute of Pathology, Essen, Deutschland
2University Hospital Essen, Department of Gynecology and Obstetrics, Essen,
Deutschland
Background: High-grade serous ovarian carcinoma (HGSOC) is the
predominant histological subtype of ovarian cancer diagnosed in clini-
cal settings. It accounts for most cancer-related deaths across all forms
of ovarian cancer. One distinguishing factor, linked to poor prognosis, is
the occurrence of myobroblast cells and extensive desmoplastic stromal
reaction (DSR). Due to frequent acquirement of therapy resistance aer
initial treatment with platinum-based components, we intent to explore
the activity of DSR-associated signaling pathways in HGSOC patients.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 255
Methods: e cohort consists of 24 platinum treated HGSOC patients
with complete clinical follow-up. RNA was isolated from paran-em-
bedded tumor samples. Digital expression analysis of genes involved in
DSR-associated pathways was performed by the NanoString nCounter
platform. Data were explored using the R programming environment
(v.4.0.3).
Result: e expression of MMP13, CGA, EPHA3, PSMD9, PITX2,
PHLIPP1 was linked to chemoresistance. Additionally, 15 genes were
directly associated with patients’ survival, including MMP13 and CGA.
Gene set enrichment analysis revealed dierent pathways linked to resis-
tance. Consistently expressed core components were mostly involved in
growth factor (TGF-ß, Ras, MAPK) as well as PI3K-Akt signaling. ese
ndings could be validated in 303 epithelial ovarian carcinomas.
Discussion: We were able to link DSR-associated pathways, marked by
increased Ras, MAPK and PI3K-Akt signaling to resistance development.
Activation of those pathways seems to be based on non-canonical TGF
signaling and increased activity of cancer-associated broblasts.
Conclusion: Since platinum-based chemotherapy still is the state-of-the-
art therapy to treat HGSOC, reasons for therapy resistance need to be
identied. is work unfolds DSR as one possible contributor. erefore,
it may be helpful to stratify HGSOC patients for DSR and consider alter-
native treatment options.
Disclosure Statement: e authors declare no conict of interest.
243
Human leukocyte antigen (HLA) typing of cancer patient-
derived xenografts (PDX) models enables personalized,
preclinical immune-oncology studies
Theresia Conrad1; Annika Wulf-Goldenberg1; Maria Stecklum1;
Michael Becker1; Simone Rhein1; Konrad Klinghammer2; Jens Homann1
1EPO Experimental Pharmacology & Oncology Berlin-Buch GmbH, Berlin,
Deutschland
2Charité University Medicine, Berlin, Deutschland
Background: In immuno-oncology research, matching of human leuko-
cyte antigen (HLA) proles of patient-derived xenogras (PDX) and com-
patible human immune cell populations is an important factor to enable
personalized, preclinical studies. With this objective, we determined indi-
vidual HLA proles of a broad panel of PDX models from 18 dierent
tumor entities and performed comprehensive HLA matching analyses of
all models and 14 peripheral blood mononuclear cell (PBMC) donors.
Methods: Based on RNA-sequencing data, HLA class I, II and non-class
types of 291 established PDX models were determined in 4-digit resolu-
tion. For comparative analyses, HLA allele and haplotype frequencies of
8862 German stem cell donors (GSCD) provided by e Allele Frequency
Net Database were used. According to donor-recipient HLA matching cri-
teria recommended by the Blood and Marrow Transplant Clinical Trials
Network, matching analyses of all PDX and 14 PBMC donor HLA proles
were performed.
Result: More than 50 % of the determined individual HLA proles show
allele homozygosity at ≥ 1 HLA class I loci. Comparisons of PDX and
GSCD HLA proles resulted in comparable frequencies of most of the
alleles and haplotypes but also in certain variations. HLA prole match-
ing analyses performed for PBMC donors and PDX models revealed 15
matches including PDX from 9 tumor entities. Exemplarily, the depen-
dence of immune therapy ecacy on matched HLA proles was shown
for a head and neck squamous cell cancer PDX humanized with PBMCs
from the patient and 3 donors.
Discussion: Interestingly, the obtained high proportions of homozygosity
and specic HLA haplotypes were likewise reported in the literature and
may serve as prognostic markers for risk and progression of cancer.
Conclusion: e generated comprehensive HLA prole portfolio contain-
ing matching information on a broad panel of PDX models and PBMC
donors supports the investigation of prognostic markers and enables per-
sonalized, preclinical immune-oncology studies to encourage the devel-
opment of novel immune-therapeutic strategies.
Disclosure Statement: e authors declare the following:
e authors eresia Conrad, Annika Wulf-Goldenberg, Maria Stecklum, Michael
Becker, Simone Rhein and Konrad Klinghammer declare no conict of interest.
Jens Homann declares the employment and the ownership of EPO Berlin-Buch
GmbH.
260
Identication of mechanisms of primary and secondary
resistance to anti-egfr and braf inhibition in brafv600e CRC
PDOS and PDX
Anna Kotarac1,2; Hiroki Osumi3; Manuela Benary4; Arndt Stahler2;
Stephan Hahn5; Sandra Liebs1; Anastasia Dielmann1; Ulrike Krueger6;
Tomasz Zemojtel6; Merve Keziban7,8; Philipp Mertins7,8; Christian Rosé9;
Frank Reichenbach9; Ryoji Yao10; Ulrich Keilholz1; Sebastian Stintzing2;
Loredana Vecchione1,2
1Charité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin,
Berlin, Germany
2Department of Hematology, Oncology, and Cancer Immunology, Campus
Charité Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany
3Department of Gastroenterology, Cancer Institute Hospital, Japanese
Foundation for Cancer Research
4BIH-Core Unit Bioinformatics, Charité - Universitätsmedizin Berlin, Berlin,
Germany
5Zentrum für Klinische Forschung (ZKF) , Ruhr-Universität Bochum, Bochum,
Deutschland
6BIH-Core Unit Genomics, Charité - Universitätsmedizin Berlin, Berlin, Germany
7Berlin Institute of Health (BIH) Core Unit Proteomics, Charité -
Universitätsmedizin Berlin, Berlin, Germany
8Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin, Germany
9Pierre Fabre Pharma GmbH, Freiburg, Germany
10Department of Cell Biology, Cancer Institute, Japanese Foundation for Cancer
Research, Tokio, Japan
Background: e combination of cetuximab (C225) and encorafenib
(LGX818) is the rst chemo free regimen approved for the treatment
of BRAFV600E mCRC patients (1). Despite of its activity, very little is
known about mechanisms of primary and secondary resistance (2,3,4).
erefore, the aim of the current work is to identify such mechanisms and
potential strategies to overcome resistance.
Methods: Ten BRAFV600E CRC patient-derived organoids (PDOs)
were treated with single agents cetuximab (C225), erlotinib (OSI-774),
encorafenib (LGX818) and irinotecan (SN-38) as well as C225+LGX818,
OSI-774+LGX818, C225+SN38 and OSI-774+SN-38 in the presence
and absence of EGF. All models were proled using whole exome DNA
sequencing, RNAseq and mass spectrometry. Moreover, RNAseq was per-
formed aer 24h of OSI-774+LGX818 in three sensitive and three resis-
tant models. Finally, ten dierent patient-derived xenogras (PDX) were
treated with single agents and combination treatments. PDXs samples
were collected before and upon progression for molecular analysis.
Results: All PDO models showed intrinsic resistance to C225, OSI-
774 and LGX818, independent of the presence of EGF. e response
to SN-38 was more variable. None of the models tested showed sensi-
tivity to C225+LGX818, while 3 out of 10 PDOs were sensitive to OSI-
774+LGX818. e molecular analysis of those models and the PDX
treatments are currently ongoing and will be presented at the conference.
Discussion: While our PDOs showed resistance towards C225, drug com-
binations with OSI-774 resulted in variable responses. e full molecu-
lar characterization of these models should help in identifying genomic
determinants of good and poor response to these treatments.
Conclusions: To the best of our knowledge, this is the rst preclinical study
using PDO and PDX models aiming to identify mechanisms of primary
and secondary resistance to the combination of anti-EGFR+LGX818.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts256
References:
1. Tabernero J et al, PMID:33503393
2. Oddo D et al, PMID:27312529
3. Middleton G et al, PMID:32047001
4. Huiberts SCFA et al, PMID:33204026
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
388
Molecular mechanisms of colorectal cancer: MACC1 and the
novel IER2 gene
Miguel Alberto1,2,3; Lenka Kyjacova4; Marc Osterland2,3;
JonathanSleeman5,6; Beate Rau1; Ulrike Stein2,3
1Charité - Universitätsmedzin Berlin, Surgical Department, Berlin, Deutschland
2Charité - Universitätsmedzin Berlin, Experimental and Clinical Research Center,
Berlin, Deutschland
3Max-Delbrück-Center for Molecular Medicine, Berlin, Deutschland
4University of Heidelberg, Medical Faculty Mannheim, Mannheim, Deutschland
5University of Heidelberg, Medical Faculty Mannheim, European Center for
Angioscience, Mannheim, Deutschland
6Karlsruher Institute for Technology, IBCS-BIP, Eggenstein-Leopoldshafen,
Deutschland
Background: e gene Metastasis Associated in Colon Cancer-1
(MACC1) is a key player for metastasis formation, tumor progression
and is a biomarker for CRC and more than 20 other solid cancer types.
Higher MACC1 expression is associated with metachronous metastasis.
Immediate Early Response 2 (IER2) is a novel player in the eld of metas-
tasis. Previous studies have linked IER2 expression with enhanced meta-
static capacities contributing to worse overall survival.
Methods: We analyzed in-silico mRNA expression proles and predictive
binding motifs for MACC1 and IER2. We made use of qRT-PCR, Western
Blot, clonogenic and proliferation assays. Furthermore, we used CRISPR-
Cas9 for creation of an IER2 knockout cell line.
Result: Cumulative survival for patients with higher expression of IER2
and MACC1 genes was signicantly worse. In-silico, both a positive
correlation between MACC1 and IER2 expression and a predicted SH3
mediated protein interaction was found. Overexpression of IER2 warrants
higher in vitro colony forming capabilities and silencing IER2 signi-
cantly hinders cellular proliferation.
Discussion: Both genes share similar roles in conferring the cell aggressive
metastatic capabilities. is synergism could be due to a SH3-mediated
protein interaction. MACC1 is a key regulator of a
HGF/cMET-mediated pro metastatic axis. IER2 is involved in CDC25A
dysregulation enhancing G1-S transitions,1 hence the heightened clono-
genic traits of the cell. Furthermore, PP2A´s substrate specicity may be
directly inuenced by IER2.1
Conclusion: MACC1, an established marker for metastatic disease and
IER2, a novel biomarker, may play an important synergetic role to con-
fer cancer cells enhanced proliferative and clone formation attributes.
e synergism between them undeniably translates into worst patient
outcomes.
Indication of source:
1. Ueda, T. et al. IER family proteins are regulators of protein phosphatase PP2A
and modulate the phosphorylation status of CDC25A. Cell. Signal. 55, 81–89
(2019).
Disclosure Statement: e authors declare no conict of interest.
405
Characterization of a novel lipase inhibitor targeting high
cancer stemness in triple-negative breast cancer (TNBC)
Hannah Grundmann1; Theresa Bozzetti1; Jasmin On1; Andrea Kulik1;
Dieter Niederacher1; Hans Neubauer1; Tanja Fehm1; Knud Esser1
1Heinrich-Heine-Universität Düsseldorf, Life Science Center, Forschungslabore
der Klinik für Frauenheilkunde und Geburtshilfe, Düsseldorf, Deutschland
Background: High cancer stemness is a main driver of TNBC malig-
nancy. However, to date the underlying pathophysiology is only partially
understood. Recently, dysregulated lipid metabolism has been suggested
to mainly contribute to TNBC stemness maintenance and pharmacolog-
ical interference with tumor cell lipid metabolism has been reported as a
promising strategy to improve cancer therapy.
Methods: We analyzed an in-house library of 2.000 compounds includ-
ing metabolically active agents by a cell-based phenotypic high-through-
put screening system to identify potentially cancer stemness reducing
agents. Reduction of cancer stem cell marker expression was quantied
by measuring the expression levels of two innovative dierentiation
markers, followed by validation with qRT-PCR and ow cytometry anal-
ysis. Furthermore, increased sensitization to treatment with Paclitaxel
and Doxorubicin was investigated by co-incubation. MDA-MB-231 and
MDA-MB-436 cells were used as in vitro model. To scrutinize lipase
expression in primary breast cancer tissue bioinformatic databases were
used.
Result: We identied a selective lipase inhibitor that specically reduced
TNBC stemness and increased sensitivity to chemotherapies. Besides
expression of the candidate lipase strongly correlated with cancer stem
cell marker expression in primary breast cancer.
Discussion: e identied lipase is highly expressed in TNBC cancer
stem cells and its activity plays an essential role in maintaining the high
cancer stem cell character of TNBC cells.
Conclusion: Pharmacological inhibition of the identied lipase may rep-
resent a new therapeutic approach for TNBC treatment and could improve
current cancer therapy due to its specic reduction of TNBC stemness.
Disclosure Statement: e authors declare no conict of interest.
416
Signaling pathways linked to activity of cancer-associated
broblasts lead to cancer progression and increased tumor
cell motility in malignant pleural mesothelioma
Michael Wessolly1; Alexander Mathilakathu1; Elena Mairinger1;
Alina Nath1; Henrik Beckert2; Daniel Kreidt1; Nick Klopp1; Balazs Hegedüs3;
Julia Steinborn1; Thomas Hager4; Robert Fred Henry Walter1;
Daniel Christian Christoph5; Jens Kollmeier6; Jeremias Wohlschlaeger4;
Thomas Mairinger7; Luca Brcic8; Sabrina Borchert1; Kurt Werner Schmid1;
Fabian Dominik Mairinger1
1University Hospital Essen, Institute of Pathology, Essen, Deutschland
2University Hospital Essen, Ruhrlandklinik-West German Lung Centre, Clinic of
Pulmonology, Division of Translational Pulmonology, Essen, Deutschland
3University Hospital Essen, Ruhrlandklinik-West German Lung Centre,
Department of Thoracic Surgery and Thoracical Endoscopy, Essen, Deutschland
4Diakonissenkrankenhaus Flensburg, Department of Pathology, Flensburg,
Deutschland
5Evangelische Huyssens Foundation Essen-Huttrop, Department of Medical
Oncology/Hematology, Essen, Deutschland
6Helios Klinikum Emil von Behring, Lungenklinik Heckeshorn, Department of
Pneumonology, Berlin, Deutschland
7Helios Klinikum Emil von Behring, Department of Tissue Diagnostics, Berlin,
Deutschland
8Medical University of Graz, Diagnostic and Research Intitute of Pathology, Graz,
Österreich
Background: Malignant pleural mesothelioma (MPM) is an aggressive,
asbestos-associated malignancy. Oen discovered in advanced tumor
stages, median survival ranges only from 9 to 15 months aer initial diag-
nosis. Unfortunately, long-term therapy responses remain unsatisfying.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 257
In recent years, research focus has shied towards the tumor microen-
vironment (TME) and its contribution to tumor development. Cancer-
associated broblasts (CAFs) are key factors within TME and are known
to exert tumor-proliferative eects. Within this study, we analysed CAF-
mediated eects on MPM cells’ behavior and activity.
Methods: MPM cell lines were subjected to conditioned medium (CM)
from activated myobroblast cell lines and vice versa. Cell viability, necro-
sis, and apoptosis rates were estimated via enzyme-activity. Cell migration
and invasion assays were used to determine tumor cells’ invasive capa-
bilities. Digital gene expression analysis was performed via NanoString
nCounter platform using a panel covering 76 CAF-associated genes.
ese in vitro generated results were veried in a clinical cohort consist-
ing of 77 MPM patients.
Result: Treated mesothelioma cells showed signs of increased invasive
capabilities, cell viability, and proliferation. KEGG pathway analysis
suggested cell cycle progression. Additionally, PI3K-Akt, MAPK, and
Ras pathways appeared highly activated. TGF-ß signaling only showed
upstream activity.
Discussion: While ligands of the TGF-ß signaling pathway were present,
SMAD signaling was inactive. Instead, it seemed that broblast CM treat-
ment enhanced non-canonical TGF-ß signaling via MAPK, PI3K-Akt and
Ras signaling.
Conclusion: e above-mentioned pathways are linked to desmoplastic
stromal reaction (DSR), a progress associated with aggressive tumor sub-
types and therapy resistance. With CAFs being key players of DSR, this
work highlights their tumor-supportive eect in vitro as well as in a clini-
cal cohort, thereby also unveiling potential therapeutic targets.
Disclosure Statement: e authors declare no conict of interest.
524
Peritoneal metastasis of colorectal cancer (pmCRC):
Identication of predictive molecular signatures by a novel
preclinical platform of matching pmCRC PDX/PD3D models
Mathias Dahlmann1,2; Guido Gambara2,3; Bernadette Brzezicha4;
Oliver Popp5; Eva Pachmayr6; Lena Wedeken7; Alina Paume7;
Margarita Mokritzkij1; Safak Gül-Klein6; Andreas Brandl6;
Caroline Schweiger-Eisbacher3; Philipp Mertins5; Jens Homann4;
Ulrich Keilholz2,3; Wolfgang Walther1; Christian Regenbrecht7,8; Beate Rau6;
Ulrike Stein1,2
1Charité - University Medicine Berlin, and Max-Delbrück-Center for Molecular
Medicine in the Helmholtz Association, Experimental and Clinical Research
Center, Translational Oncology of Solid Tumors, Berlin, Deutschland
2German Cancer Consortium, Heidelberg, Deutschland
3Charité – Universitätsmedizin Berlin, Charité Comprehensive Cancer Center,
Berlin, Deutschland
4EPO GmbH Berlin-Buch, Berlin, Deutschland
5Max-Delbrück-Center for Molecular Medicine and Berlin Institute of Health,
Proteomics Platform, Berlin, Deutschland
6Charité - University Medicine Berlin, Department of Surgery, Berlin,
Deutschland
7CELLphenomics GmbH, Berlin, Deutschland
8University Medicine Göttingen, Institute of Pathology, Göttingen, Deutschland
Background: Peritoneal metastasis of colorectal carcinoma (pmCRC)
occurs in approximately 15% of CRC patients, behaves clinically distinct
from hematogenous spread. Predictive molecular signatures to medi-
cal treatments have not yet been dened. e aim of the study was the
establishment and characterization of matched patient-derived xenogra
(PDX) and patient-derived 3D cell culture (PD3D) models from surgical
samples of pmCRC patients for individualized therapy concept to improve
outcome of pmCRC patients and to dene signatures to better guide ther-
apy selection.
Methods: pmCRC metastases were obtained during routine surgery
and used to generate matched PDX/PD3D models, which were treated
with Standard-of-Care (SoC) regimen and targeted drugs, while growth
response was monitored. All sample types were molecularly characterized
by multi-omics technologies to identify putative predictive biomarkers.
Result: 14 pmCRC PDX models, including 9 matched PD3D/PDX mod-
els were established. Preclinical treatment response to 17 SoC and targeted
therapies were integrated with multi-omics data and resulted in predic-
tive biomarkers for 10 treatment options. Of note, enrichment of BRCA2
mutations in the pmCRC samples pointed to the use of PARP inhibitors
as novel two-hit combination therapy, in which combination of olapa-
rib with 5-FU or trametinib strongly improved the response of our PDX
models resistant to respective monotherapy.
Discussion: Patterns of gene/protein expression, coding mutations, and
protein phosphorylation of pmCRC metastases and their derived PD3D/
PDX models correlated well. Data integration revealed altered cellular
processes and signaling pathways impacting therapy response as basis to
molecularly tailor new therapies.
Conclusion: e novel preclinical drug testing platform of matched
pmCRC models, characterized by multi-omics, facilitated the identica-
tion of predictive biomarkers and cancer relevant signatures for ecient
and novel drug combinations to improve the outcome in pmCRC therapy,
ready for validation in clinical cohorts.
Reference:
Dahlmann et al., Mol Cancer, accepted September 2021
Disclosure Statement: e authors declare no conict of interest.
537
The CCCMLMU Molecular Tumorboard: clinical and molecular
characteristics of the rst 1000 patients
Kathrin Heinrich1,2; Lisa Miller-Phillips1,2; Frank Ziemann1,2;
Korbinian Hasselmann1; Katharina Rühlmann2;
Michael von Bergwelt-Baildon1,2; Julian Holch1,2; Tobias Herold1,2,3;
Louisa von Baumgarten2,4; Philipp Greif1,2,3; Irmela Jeremias3,5;
Fabian Trillsch2,6; Rachel Würstlein2,6,7; Andreas Jung2,8; Thomas Kirchner2,8;
Frederick Klauschen3,8,9; Klaus Metzeler10,11; Volker Heinemann1,3,9;
Benedikt Westphalen1,3,9
1Medizinische Klinik und Poliklinik III, LMU Klinikum München, München,
Deutschland
2Comprehensive Cancer Center, LMU Klinikum München, München,
Deutschland
3German Cancer Consortium (DKTK), Partner Site Munich, München,
Deutschland
4Neurologische Klinik und Poliklinik, LMU Klinikum München, München,
Deutschland
5Department of Apoptosis in Hematopoietic Stem Cells, Helmholtz Center
Munich, German Center for Environmental Health (HMGU), München,
Deutschland
6Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, LMU Klinikum
München, München, Deutschland
7Brustzentrum, LMU Klinikum München, München, Deutschland
8Pathologisches Institut, Ludwig-Maximilians-Universität München, München,
Deutschland
9Comprehensive Cancer Center (CCC), LMU Klinikum München, München,
Deutschland
10Klinik und Poliklinik für Hämatologie, Zelltherapie und Hämostaseologie,
Universitätsklinikum Leipzig, Leipzig, Deutschland
11German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ),
Heidelberg, Deutschland
Purpose: In 2016, the University of Munich Molecular Tumor Board
(MTB) was implemented to initiate a precision oncology program. is
review of cases was conducted to assess clinical implications and func-
tionality of the program, to identify current limitations and to inform
future directions of these eorts.
Methods: Charts, molecular proles and tumor board decisions of the
rst consecutive 1000 cases (01/2016 – 03/2020) were reviewed.
Results: Of the rst 1000 patients presented to the MTB, 914 patients
received comprehensive genomic proling (CGP). Median age of patients
was 56 years and 58% were female. Patients with 90 dierent malignan-
cies were enrolled in the program. e most prevalent diagnoses were
breast (16%) and colorectal cancer (10%). Dierent types of gene panels
have been used; most of them available through the local department of
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts258
pathology. Testing was technically successful in 88%. In 41% of cases, an
alteration triggered a therapeutic recommendation. e most frequent
actionable alterations were: FGFR alterations (8%), tumour mutational
burden (TMB - 7%) and MET alterations (6%). e most frequent non-ac-
tionable alterations were KRAS (%) and TP53 (%). Frequency of therapy
recommendations diered signicantly in between malignancies ranging
from over 50% in breast or biliary tract cancer to less than 30% in pancre-
atic cancer. Based on this chart review, 17% of patients received treatment
based on the MTB recommendation.
Discussion and Conclusions: e University of Munich precision oncol-
ogy program serves as a clinical platform for caregivers from a variety
of departments. Based on these results, patients with certain malignan-
cies (breast and biliary tract cancer) tend to derive more benet from
enrolment in a precision oncology program. e low rate of just 17%
therapeutic implementation of MTB recommendations underscores the
importance of optimizing the clinical use of CGP. Access to targeted ther-
apies outside of clinical trials and patient selection remain major obstacles
in precision oncology.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
561
Assessing the residual activity of germ-line BRCA2 mutations
by novel malignancy risk prediction score
Ivana Radulovic1, Michael Schündeln1, Lisa Müller2, Johannes Ptok2,
Ellen Honisch3, Dieter Niederacher3, Heiner Schaal2, Constanze Wiek4,
Helmut Hanenberg1 4
1Department of Pediatrics III, University Hospital Essen, University of Duisburg-
Essen, Essen, Deutschland
2Institute of Virology, University Hospital Düsseldorf, Heinrich Heine University
Duesseldorf, Duesseldorf, Deutschland
3Department of Gynecology and Obstetrics, University Hospital Düsseldorf,
Heinrich-Heine University Düsseldorf, Düsseldorf, Deutschland
4Department of Otorhinolaryngology & Head/Neck Surgery, University Hospital
Düsseldorf, Heinrich Heine University, Düsseldorf, Deutschland
Background: BRCA2 is an essential DNA repair gene that is frequently
mutated in pedigrees with breast, ovarian and pancreatic cancers. Bi-allelic
germ-line mutations in BRCA2 occur in a rare pediatric inherited disor-
der, Fanconi anemia (FA) subtype FA-D1, that is clinically characterized
by congenital abnormalities and an extremely high propensity to develop
malignancies. As no living organism with a complete loss of BRCA2 pro-
tein function exists, we hypothesized that the clinical manifestation of
malignancies in these children can be used to assess residual function(s)
of mutated BRCA2 allels.
Methods: To develop an algorithm predicting the clinical phenotype of
BRCA2 mutations, data from published FA-D1 patients with bi-allelic
BRCA2 mutations were used in a novel scoring system: alleles with frame-
shi/stop codon mutations were assigned 0 and with missense mutations
+1 points. Alleles with mutations downstream of exon 11 received +1.
e MaxEnt and HBond splicing scores were used to assign 0 points to a
severe and +1 to a mild splice disturbation. Points from both alleles were
then correlated with dierent clinical parameters of the malignancies.
Result: 70 FA-D1 patients had a lifetime cancer risk of 92.9% with 1-4
malignancies. We could distinguish 3 risk groups (scores: 0, 1, >1), with
median ages of cancer of 1.3, 3.05 and 4.9 years, associated with median
OS of 2.3, 4.9 and 17.0 years, respectively.
Discussion: Our algorithm predicts residual functions of mutated BRCA2
alleles in humans, strongly inuencing the manifestation of malignancies.
Conclusion: To validate the algorith, the scores/mutations should be
correlated with cancer manifestations of heterozygous germ-line BRCA2
carriers and mutant proteins experimentally tested in engineered human
FA-D1 cells.
Disclosure Statement: e authors declare no conict of interest.
563
Mapk inhibition in combination with vinorelbine might
represent a new therapeutical option for brafv600e CRC
Anna Kotarac1,2; Hiroki Osumi3; Sandra Liebs1; Anastasia Dielmann1;
Ryoji Yao4; Ulrich Keilholz1; Sebastian Stintzing2; Loredana Vecchione1,2
1Charité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin,
Berlin, Germany
2Department of Hematology, Oncology, and Cancer Immunology, Campus
Charité Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany
3Department of Gastroenterology, Cancer Institute Hospital, Japanese
Foundation for Cancer Research, Tokio, Japan
4Department of Cell Biology, Cancer Institute, Japanese Foundation for Cancer
Research, Tokio, Japan
Background: BRAFV600E colon cancer (CRC) cell lines were observed
to be extremely sensitive to vinorelbine (VBN) (1). A subsequent phase
II study could not conrm these results (2). e multidrug resistant phe-
notype, driven by the expression of P-glycoprotein and regulated by the
mitogen activated protein kinases (MAPK) pathway (3), is a well-known
intrinsic mechanism of VBN resistance and could have resulted in the
negative phase II study. Here, we investigated if combining VBN with
anti-Epidermal Growth Factor Receptor (EGFR) together with MAPK
inhibitors increases its activity in CRC cell lines and patient derived
Organoids (PDOs).
Methods: ree BRAFV600E CRC cell lines were treated with VBN
alone or in combination with cetuximab (C225) + encorafenib (LGX818).
Moreover, ten BRAFV600E CRC PDOs were treated with single agent
VBN; PDOs with higher VBN IC50 were treated with VBN in combina-
tion with erlotinib (OSI-774) + LGX818.e expression of pEGFR, pAKT,
pERK, P-glycoprotein and cleaved PARP was tested both in cell lines and
PDOs aer 24, 48, and 72h.
Results: e addition of C225+LGX818 to VBN resulted in a signicantly
lower IC50 (13.7-17,500-fold change) than VBN alone in all tested CRC cell
lines. All PDOs were sensitive to VBN alone. Treating the two PDOs with
highest VBN IC50 with the triple combination of VBN+OSI-774+LGX818
resulted in a signicantly lower IC50 (6-180-fold change) than VBN
alone. Treatment with MAPK inhibitors reduced P-glycoprotein expres-
sion already aer 24 h. e addition of C225+LGX818 to VBN showed a
signicant increase of cleaved PARP as compared to C225+LGX818 and
VBN alone. Similar results were obtained in PDOs.
Discussion: e addition of C225+LGX818 to VBN signicantly
increased the activity of VBN in both BRAFV600E CRC cell lines and
PDOs. is phenotype is due to the P-glycoprotein reduction through the
MAPK pathway inhibition.
Conclusions: e triple combination represents a promising treatment
option for BRAFV600E mCRC patients.
References:
1. Vecchione L et al PMID:27058664
2. Cremolini C et al PMID:29209533
3. Katayama K. et al PMID:17620438
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
603
Larger ectosome-like EVs mirror the pattern of surface
markers on malignant cells: a cell line-based study
Hari Gorantla1; Vijay Boddu2; Nikolas von Bubno2; Frank Gieseler2
1UKSH Campus Lübeck, Klinik für Hämatologie und Onkologie, Molekulare
Therapie, Lübeck, Deutschland
2Klinik für Hämatologie und Onkologie, UKSH Campus Lübeck, Lübeck,
Deutschland
e presence of reliable biomarkers in the diagnosis and treatment of
malignant diseases is a long-held wish for oncologists, especially in the
treatment of solid tumors, where histological biopsies might be necessary
otherwise. As we learn more about the genetic characteristics, the proof
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 259
of the corresponding mutations in tumor cell-derived genetic material
found in the plasma and in extracellular vesicles (EVs) is a promising way.
During the preparation and enrichment of smaller exosome-like EVs for
the analysis of incorporated genetic material, the larger ectosome-like ves-
icles are regularly discarded aer the high-speed centrifugation step. We
and others think that this is a waste of valuable biological material for at
least two reasons: (1) the preparation of larger ectosomes is, due to their
bigger size, more specic and (2) due to their biogenesis by blebbing of
the outer membrane ectosomes might mirror the membrane components
of the parental cell.
In this project, we examined potentially biological relevant surface
markers of leukemia cell lines, having known genetic mutations, as well as
two bladder cancer cell lines with dierent biological properties (muscle
invasive and non-invasive), and compared them with their correspondent
larger ectosome-like EVs. We found, (1) that the preparation of larger
ectosome-like EVs by sequential centrifugation is highly specic, and
(2) that ectosomes indeed reect and mirror the membrane markers of
their parental cells in many cases. Although this is an in-vitro study using
cell lines, we think that the results are noteworthy and might serve as a
proof-of-principles study, as we show that larger ectosome-like EVs can be
prepared with high selectivity using the described methods, and that they
might be used as surrogate markers in biomaterial from patients, such
as blood or urine. Further studies might show the functional relevance,
e.g. for the forming of the tumor micro-environment by EVs released by
malignant cells.
Disclosure Statement: e authors declare no conict of interest.
605
MEK1 mediated essential tyrosine phosphorylation of MACC1
is druggable to eciently restrict colorectal cancer metastasis
Dennis Kobelt1,2; Daniel Perez-Hernandez3,4; Claudia Fleuter1;
Mathias Dahlmann1,2; Fabian Zincke1; Janice Smith1; Rebekka Migotti3;
Oliver Popp3; Susen Burock5; Wolfgang Walther1; Gunnar Dittmar3,4;
Philipp Mertins3; Ulrike Stein1,2
1Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin
and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association,
Translational Oncology of Solid Tumors, Berlin, Deutschland
2German Cancer Consortium (DKTK), Heidelberg, Deutschland
3Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association,
Mass Spectrometry Core Unit, Berlin, Deutschland
4Luxembourg Institute of Health, Proteome and Genome Research Laboratory,
Strassen, Luxemburg
5Charité - Universitätsmedizin Berlin, Charité Comprehensive Cancer Center,
Berlin, Deutschland
Background: Cancer metastasis causes >90% of cancer deaths and
remains a major treatment challenge. We deciphered the impact of tyro-
sine phosphorylation of MACC1, a causative driver for cancer metas-
tasis, for cancer cell signaling and novel interventions to restrict cancer
metastasis.
Methods: e MEK1/MACC1 axis was identied by mass spectrometry
(MS). MACC1 tyrosine phosphorylation sites were identied by in sil-
ico predictions, and validated by quantitative SRM-MS and site-directed
mutagenesis. MEK1 phosphorylation of MACC1 was functionally tested
in vitro and in mice regarding CRC cell motility, proliferation and metas-
tasis, and in human CRC specimens.
Result: We identied MACC1 as new MEK1 substrate. MEK1 directly
phosphorylates MACC1, leading to accelerated and increased ERK1 acti-
vation. Mutating in silico predicted hierarchical MACC1 tyrosine phos-
phorylation sites abrogates MACC1-induced migration, invasion and MET
expression, a transcriptional MACC1 target. Targeting MEK1 by RNAi or
clinically applicable MEK1 inhibitors AZD6244 and GSK1120212 reduces
MACC1 tyrosine phosphorylation and restricts MACC1-induced metas-
tasis formation in mice. Although MEK1 levels, contrary to MACC1, are
not of prognostic relevance for CRC patients, MEK1 expression was found
indispensable for MACC1-induced metastasis.
Discussion: is study identies MACC1 as new MEK1 substrate for
tyrosine phosphorylation decisively impacting cell motility, tumor growth
and metastasis. us, MAP kinase signaling is not linear leading to ERK
activation, but branches at the level of MEK1. is fundamental nding
opens new therapeutic options for targeting the MEK1/MACC1 axis as
novel vulnerability in patients at high risk for metastasis.
Conclusion: e ndings shown for CRC might be translated to further
solid tumor types. e usefulness of MACC1 as therapeutic target towards
MEK1 inhibitor treatment requires conrmation in clinical trials.
Indication of source:
1 Oncogene. 2021 Aug;40(34):5286-5301.
Disclosure Statement: e authors declare no conict of interest.
622
Cancer-associated broblasts regulate kinase activity in
mesothelioma cell lines via paracrine signaling and thereby
dictate cell faith and behavior
Fabian Dominik Mairinger1; Alexander Mathilakathu1; Michael Wessolly1;
Elena Mairinger1; Hendrik Beckert2; Daniel Kreidt1; Luka Brcic3;
Julia Steinborn1; Kristina Greimelmaier4; Jeremias Wohlschlaeger4;
Kurt Werner Schmid1; Sabrina Borchert1
1Institute of Pathology, University Hospital Essen, Deutschland
2Department of Pulmonary Medicine, University Hospital Essen, Essen,
Deutschland
3Diagnostic and Research Institute of Pathology, Medical University of Graz,
Graz, Österreich
4Department of Pathology, Diakonissenkrankenhaus Flensburg, Flensburg,
Deutschland
Background: Malignant pleural mesothelioma (MPM) is a rare type of
cancer with an infaust prognosis despite multimodal therapy. MPM cells
modulate the immune response to their benet. ey release proinam-
matory cytokines, such as TGF-ß, awakening resting brocytes that switch
their phenotype into activated broblasts. Signaling interactions between
cancer cells and cancer-associated broblasts (CAFs) play an integral part
in tumor progression. is study aimed to investigate the role CAFs play
in MPM progression, analyzing the impact this complex, symbiotic inter-
action has on kinase-related cell signaling in vitro.
Methods: We simulated paracrine signaling in vitro by treating MPM
cell lines with conditioned medium (CM) from broblasts (FB) and vice
versa. NCI-H2052, MSTO-211H, and NCI-H2452 cell lines representing
the three mayor MPM subtypes, while embryonal myobroblast cell lines,
IMR-90 and MRC-5, providing a CAFs-like phenotype. Subsequently,
dierences in proliferation rates, migratory behavior, apoptosis, necrosis,
and viability were used as a covariate for data analysis. Kinase activity of
treated samples and corresponding controls were then analyzed using the
PamStation12 platform (PamGene).
Result: Treatment with myobroblast-derived CM revealed signicant
changes in phosphorylation patterns in MPM cell lines. e observed
eect diers strongly between the analyzed MPM cell lines and depends
on the origin of CM. Overall, a much stronger eect was observed using
CM derived from IMR-90 than MRC-5. e phosphorylation changes
mainly aected the MAPK signaling pathway.
Discussion: e factors secreted by myobroblasts in broblasts CM sig-
nicantly inuence the phosphorylation of kinases, mainly aecting the
MAPK signaling cascade in tested MPM cell lines.
Conclusion: Based on our in vitro results, the use of MEK or ERK inhibi-
tors could have a positive synergistic eect with cisplatin-based treatment,
potentially improving clinical outcomes for MPM patients.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts260
684
Co-culture of patient-derived tumor organoids with
autologous immune cells for therapy response prediction
Alina Paume1; Samantha Exner1; Jürgen Loskutov1;
Christoph Reinhard1,2; Christian Regenbrecht1,2,3
1CELLphenomics GmbH, Berlin, Deutschland
2ASC Oncology GmbH, Berlin, Deutschland
3University Hospital Göttingen, Department for Pathology, Göttingen,
Deutschland
Background: Cancer research is increasingly focusing on immunother-
apies such as immune checkpoint inhibitors that activate the patient’s
immune system by PD-L1 or CTLA-4 inhibition to specically target the
tumor. is requires appropriate and clinically relevant in vitro tumor
models to assess the eciency of these novel drugs not only for preclinical
drug development, but for therapy prediction on the individual patient’s
level.
Methods: Autologous PBMCs were co-cultured with corresponding 3D
patient-derived tumor organoids in presence or absence of additional
immune checkpoint inhibitors such as Nivolumab, Pembrolizumab or
Ipilimumab. eir interaction and the inuence on tumor cell viability
and apoptosis was investigated by proliferation and FACS analysis.
Results: We developed a short-term co-culture assay and applied it to 10
dierent models of dierent entities including melanoma, colon cancer
and sarcoma. Analysis of the basal PBMC viability revealed diverging pat-
terns of activation or suppression, which could be modulated by addition
of immune checkpoint inhibitors.
Discussion: Our assay aims at representing the tumoral and immunolog-
ical characteristics of the patient using autologous 3D co-culture models
without additional immune cell stimulation. e focus lies on a straight-
forward workow, the results of which can be easily integrated into the
overall clinical picture and the subsequent therapeutic decision. In addi-
tion, deeper tumor expression analyses of MHC I/II, PD-L1 and CTLA-4
is necessary for a better understanding of tumor evasion and development
of eective counter strategies.
Conclusions: Further development of patient-specic co-culture screen-
ing approaches is essential for immune therapy prediction. In that way,
responders could be selected from non-responders in advance, treatment
responses improved, and valuable time and costs saved.
Disclosure Statement: e authors declare the following:
Christian Regenbrecht is shareholder at CELLphenomics GmbH, a company
oering drug screens on organoid models, and ASC Oncology GmbH, a company
involved in patient specic therapy prediction. Christoph Reinhard is shareholder
at ASC Oncology GmbH.
711
TP53-dependent release of extracellular vesicles (EVs) from
urological malignancies aects functional status of tumor
associated macrophages and therapy response
Barbara Köditz1, Elena Izquierdo2, Tim Nestler1, Michael Hallek2,
AxelHeidenreich1, Melanie von Brandenstein1, Christian Pallasch2
1Uniklinik Köln, Urologie, Köln, Deutschland
2Uniklinik Köln, Innere Medizin I, Köln, Deutschland
Background: Immune evasion is one of the hallmarks of cancer and one
of the most important strategies for tumor survival. One mediator, which
can induce immune evasion and therefore tumor survival, are extracellu-
lar vesicles (EVs). EVs can be secreted by tumor cells and are “mini-maps
of the secreting cell. Here the question was if EVs derived from tumor cells
with dierent TP53 status can have an impact on macrophage activation
and therefore on phagocytosis of tumor cells.
Methods: EVs from two prostate cancers (PC3 and LNCap), bladder car-
cinoma (HTB-9) and seminoma (TCam2) were investigated. e impact
of EVs on phagocytosis was analyzed by an antibody dependent cellu-
lar phagocytosis (ADCP). In order to understand the role of PD-L1 and
CD47 in this mechanism, EVs were pretreated with Anti-PD-L1 and
Anti-CD48 and further investigated in an ADCP. To proof the principle of
the role between EVs and PD-L1, CRISPR-KO of PD-L1 and RAB27A in
PC3 cells were established and isolated EVs analyzed via an ADCP.
Result: EVs derived from cancer cells with dierent TP53 status can have
an impact on macrophage activation and therefore on phagocytosis of
tumor cells. EVs derived from TP53 null cell line (PC3) cause a signi-
cant decrease of phagocytosis, compared to TP53 wild type (LNCap and
Tcam2) and to the control. To investigate the role PD-L1 and CD47 were
blocked on the EVs. In the case of blockage of PD-L1 on PC3 derived EVs
cause signicant increase on phagocytosis performed by macrophages.
Furthermore the blockage of PD-L1 and Rab27A in PC3 cells cause a sig-
nicant increase in macrophage activation.
Discussion: Based on the results, it could be seen, that EVS has an impact
on macrophage activation and therefore on the phagocytosis of tumor
cells. On the other hand, also the p53 status of the tumor cell seem to have
an impact.
Conclusion: It could be concluded that EVs derived from tumor cells with
dierent TP53 status can have an impact on macrophage activation in the
presence of exosomal PD-L1 and therefore on the therapy response.
Disclosure Statement: e authors declare no conict of interest.
715
Novel Androgen receptor truncation in Cologne collective
Melanie von Brandenstein; Manuel Huerta; Ermila Spahic;
BarbaraKoeditz; Sina Wagner; Axel Heidenreich
University Hospital of Cologne, Clinic and Polyclinic for Urology, Cologne,
Deutschland
Background: e HSD3B1 SNP at position 1245 is responsible for
resistance to androgen-deprivation therapy (ADT) in prostate cancer.
According to the literature it seems, that not only the mutation is respon-
sible for resistance to ADT in prostate cancer. A further possible expla-
nation of failed ADT can be a truncation or mutation of the androgen
receptor (AR). Several dierent mutations of the AR are already known,
nevertheless, we identied a novel truncated AR, called AR/TC. It was
possible to identify a hypothetical miR/DNA binding site.
Methods: We isolated the cfRNA from blood (n=90) and performed SNP
PCR and qRT-PCR for the identication of the novel truncated AR. We
analyzed our collective on the presences and distribution of heterozygotes
vs homozygotes (n=50). erefore, we isolated the cfDNA from blood
samples and established a SNP PCR. Since the hypothesized truncation
of the AR is only present on RNA level, we isolated the RNA form blood
and performed qRT-PCR.
Result: e distribution of heterozygotes to homozygotes was 50%. Even
in our group of castration-resistant PCa there was a distribution of 50%.
Furthermore, the novel truncated AR was present in all patients in the
group of castration-resistance. Signicant dierences were detectable by
comparing the group of castration-resistance patients with patients who
were diagnosed with high risk or intermediate prostate cancer.
Discussion: According to the identication of a novel truncated AR fur-
ther experiments needed.
Conclusion: It seems to be of great importance to screen all patients
regarding the HSD3B1 mutation. Whether the newly identied AR/TC
is responsible for castration-resistance or whether the ADT increases the
miR and therefore leads to an overproduction of the AR/TC needs to be
proven in detail.
Disclosure Statement: e authors declare no conict of interest.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 261
740
Single Cell RNA Sequencing Workow for Circulating Tumor
Cells in Metastatic Breast Cancer Research
Anna Abramova; André Franken; Mahdi Rivandi; Liwen Yang;
EllenHonisch; Dieter Niederacher; Tanja Fehm; Hans Neubauer
Department of Obstetrics and Gynecology, University Hospital and Medical
Faculty of the Heinrich-Heine-University Duesseldorf, Düsseldorf, Deutschland
Background: Circulating tumor cells (CTCs) can act as an analyte of a
non-invasive liquid biopsy. Despite their rare presence in the cancer
patients’ blood their potential as a prognostic and predictive biomarker
forces the medical research to establish sensitive methods for clinical anal-
ysis. In this context, we have implemented a single cell RNA sequencing
workow on breast cancer (BC) cell line cells adapted to conditions of
CTCs.
Methods: Non-xed BC cell line cells (luminal MCF7 and triple-nega-
tive MDA-MB-231) were spiked into healthy donors’ blood samples and
enriched with the CellSearch system followed by suspension staining
using an antibody cocktail against EpCAM, MUC1, HER2/neu, and CD45
as well as the dye Annexin V to detect early apoptotic cells. Single cells
were picked with the CellCelector system followed by library preparation
using the QIAseq UPX 3‘ Transcriptome Kit. Sequencing was performed
on the MiSeq system.
Result: e use of an EpCAM, MUC1 and HER2/neu antibody cocktail
increased the identication rate of CTCs from patients with luminal BC
compared to each antibody alone. e additional discrimination of early
apoptotic cells by Annexin V improved the quality of selected single cells,
which was mirrored by a 16-fold RNA yield and increased transcript
diversity as well as higher read numbers and the presence of mapped reads
for ACTB and GAPDH. By comparing MCF7 and MDA-MB-231 cells, we
were able to dierentiate both cell lines on single cell level and observed
the expected dierences in the expression of e.g. EPCAM, KRT8/18/19,
CD24, VIM, ADAM8/19, ANKRD1, and AXL. Spiking MCF7 cells into
healthy donors’ blood samples and processing with our workow did not
impair the data quality compared to non-processed cells (R = 0.8).
Conclusion: We implemented a single cell RNA sequencing workow
including careful preanalytical detection of high-quality cells, which will
strongly improve CTC analysis for a clinical setting.
Disclosure Statement: e authors declare no conict of interest.
752
Impact of the sequence of modern combination
chemotherapy protocols on survival of patients with
advanced pancreatic cancer treated at the West German
Cancer Center Essen
Julius Röhrle1; Andreas Paul2,3; Peter Markus4; Brigitte Schumacher5; David
Albers5; Johanna Wendling1; Saskia Ting6; Bastian Mende7; Marlene
Massmann1; Isabel Virchow1; Vivian Rosery1; Katharina Laue1; Gregor
Zaun1,8; Karina Kostbade1; Michael Pogorzelski1; Sven-Thorsten Liers1,8;
Kurt Werner Schmid3,6; Hans-Ulrich Schildhaus3,6; Martin Schuler1,3; Stefan
Kasper-Virchow1,3; Jens Siveke1,3,8; Marcel Wiesweg1
1West German Cancer Center, Department of Medical Oncology, University
Hospital Essen, Essen, Deutschland
2West German Cancer Center, Department of General, Visceral and Transplant
Surgery, University Hospital Essen, Essen, Deutschland
3German Cancer Consortium (DKTK), Partner site University Hospital Essen,
Essen, Deutschland
4Elisabeth Hospital Essen, Department of General Surgery and Traumatology,
Essen, Deutschland
5Elisabeth Hospital Essen, Department of Gastroenterology, Essen, Deutschland
6West German Cancer Center, Institute of Pathology Essen, University Hospital
Essen, Essen, Deutschland
7Central Pharmacy, University Hospital Essen, Essen, Deutschland
8Bridge Institute of Experimental Tumor Therapy, West German Cancer Center,
University Hospital Essen, Essen, Deutschland
Introduction: Pancreatic ductal adenocarcinoma (PDAC) is one of the
most deadly cancers. In clinical studies modern combination therapy
protocols such as FOLFIRINOX or gemcitabine/nab-paclitaxel (G/nP)
demonstrated superior survival outcomes over monochemotherapies.
In clinical practice, many pts receive a sequence of both regimens as
rst- and second-line palliative treatment. However, there is no guidance
regarding a preferred order.
Methods: We retrospectively analyzed the clinical outcome of patients
with PDAC treated at the West German Cancer Center Essen, an
Oncology Center of Excellence designated by the Deutsche Krebshilfe,
from 2014 to 2020. Patient data and treatments were retrieved from the
hospital information system. Endpoints included overall survival (OS),
progression-free survival (PFS) and overall response rates (ORR) for all
treatment lines as well as disease-free survival (DFS) for curatively treated
patients.
Results: We identied 170 patients with available follow-up. Of those,
146 (85%) pts received palliative CTX for metastatic or locally advanced
PDAC. Median OS in this group was 8.2 months (95% CI 6.9-9.7). 24
patients (15%) underwent curatively intended surgical resection, of which
21 relapsed. Median DFS in resected patients was 14.1 (12.0-21.5) months,
and median OS 27.7 (21.4-NE) months. Median PFS upon rst palliative
chemotherapy was 4.1 (3.1-6.0) months. In patients who received at least
two lines of therapy, rst-line treatment with FOLFIRINOX did not trans-
late into superior OS as compared to alternative multiagent protocols
including G/nP (median OS 12.1 months [9.5-18.5] vs. 12.0 [9.7-16.9]).
Second-line regimens had similar PFS (overall log-rank p=0.85, median
PFS2 2.3 [1.8-2.9], per-regimen median between 1.8 and 3.9 months).
Prolonged survival times were observed in individual pts, which associ-
ated with unique genomic features enabling targeted treatment options.
Conclusions: e choice of rst-line chemotherapy, FOLFIRINOX or
G/nP, had no impact on survival outcomes of this real-world cohort of
PDAC patients.
Disclosure Statement: e authors declare no conict of interest.
792
Molecular characterization of biliary tract cancers treated at
the West German Cancer Center Essen
Timm Reißig1,2,3,4; Ilektra-Antonia Mavroeidi3; Melanie Guyot3,5;
Sven-Thorsten Liers1,2,4; Thomas Herold4,6; Stefan Kasper-Virchow3,4;
Martin Schuler3,4; Andreas Paul4,7; Hans-Ulrich Schildhaus4,6;
Jens Siveke1,2,3,4
1Bridge Institute of Experimental Tumor Therapy, West German Cancer Center,
University Hospital Essen, Essen, Deutschland
2Division of Solid Tumor Translational Oncology, German Cancer Research
Center (DKFZ), Heidelberg, Deutschland
3Department of Medical Oncology, West German Cancer Center, University
Hospital Essen, Essen, Deutschland
4German Cancer Consortium (DKTK), Partner Site University Hospital Essen,
Essen, Deutschland
5Department of Gastroenterology, Oncology and Hematology, Diabetology and
Rheumatology, Marien-Hospital Wesel, Wesel, Deutschland
6Institute of Pathology, West German Cancer Center, University Hospital Essen,
Essen, Deutschland
7Department of General, Visceral and Transplantation Surgery, University
Hospital Essen, Essen, Deutschland
Background: Next to their anatomic presentation, biliary tract cancers
(BTC) are dened by distinct molecular features, which enable an increas-
ing number of targeted treatment options. We here describe the muta-
tional landscape of a BTC cohort with particular focus on DNA damage
repair (DDR) systems.
Methods: We retrospectively analyzed the clinical outcome and mutational
status of patients with BTC treated at the West German Cancer Center
Essen from 2016 to 2020. Patient data and treatments were retrieved from
the hospital information system. We performed two targeted DNA-based
assays (customized NGS panel and AmoyDx® HRD Focus Panel) and one
RNA-fusion assay (FusionPlex CTL Panel [Archer]). Survival and addi-
tional clinical endpoints were associated with the mutational status.
Results: We analyzed 55 patients including 35 intrahepatic cholangio-
carcinoma (iCCA, 64%), 12 perihilar CCA (pCCA, 22%), 5 distal CCA
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Oncol Res Treat 2022;45(suppl 1):7–284 Abstracts262
(dCCA, 9%) and 3 gallbladder cancers (GBC, 5%) with both DNA-based
assays. e most commonly mutated genes were TP53 (17/55, 31%),
KRAS (13/55, 24%), ARID1A, BAP1, IDH2 and PIK3CA (each 5/55, 9%).
Alterations in the DDR pathway genes were detected in 4 patients (4/55,
7.3%). Additionally, 14 samples were analyzed with the RNA-fusion assay.
We identied four FGFR2 fusions (with dierent fusion partners, 4/55,
7.3%) and one NRG1 fusion (1/55, 1.8%). Association with clinical data
will be reported at the meeting.
Conclusion: We report a well-characterized cohort of BTC patients ana-
lyzed with three molecular assays. e 7% of BTC patients with DDR
deciency might be another subgroup suitable for targeted therapies, i.e.
PARP inhibition.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
933
The impact of CD4+T cell plasticity in colorectal cancer on
immunotherapeutic strategies
Leonie Konczalla1,2; Filippo Cortesi1; Tabea Sturmheit3; Yogesh Kumar1;
Ramez Wahib1; Jenny Krause4; Anastasious Giannou1; Nathaniel Melling1;
Daniel Perez5; Jakob Izbicki1; Samuel Huber4; Nicola Gagliani1,4
1University Medical Center Hamburg-Eppendorf, Department of General,
Visceral and Thoracic Surgery, Hamburg, Deutschland
2niversity Medical Center Hamburg-Eppendorf, Mildred Scheel Cancer Career
Center , HaTriCS4, Hamburg, Deutschland
32cureX A/S, København, Dänemark
4University Medical Center Hamburg-Eppendorf, Centre for Internal Medicine, I.
Department of Medicine, Hamburg, Deutschland
5Asklepios Klinik Altona, Hamburg, Deutschland
Background: Immune cells play a pivotal role in the tumorigenesis as well
as in therapy. Despite extensive research, the role of Foxp3+TREGas well as
TH17 cells is still debated. However, with regard to combating cancer with
immunotherapies, the division in tumorpromoting and -inhibiting cells
is becoming increasingly important to pave the way for ecient therapy.
Methods: Human single-cell RNAseq was combined with cutting-edge
mouse models to dissect function and developmental trajectory of
IL-17A+Foxp3+CD4+T cells in CRC.
Result: In an unsupervised analysis of human and murine CD4+T cells,
we noticed a large proportion of IL-17A+CD4+T cells, also express-
ing the hallmark feature of TREG, forkhead box P3 (Foxp3). Our murine
data show strong tumor-fostering activity of IL17A+FoxP3+CD4+T cells.
Cellular trajectory was unveiled by RNAseq of human tumor-inl-
trating T-cells and T cell receptors. Interestingly, these data revealed
the ability of Foxp3+T
REG to perform a full conversion to TH17 and
IL-17A+Foxp3+CD4+T cells. However, classical TH17 cells were not able
to convert to IL-17A+Foxp3+CD4+T cells. Importantly, our data suggested
that trajectory is regulated by co-inhibitory receptor expression.
Discussion: In CRC IL-17A+Foxp3+CD4+T cells are present, which are
pro-tumorigenic while suppressing inammation. is stands in contrast
to the long-believed causality of inammation and tumor growth. One
reason for these discordant functions may be the dierent cellular pre-
cursors of IL-17A+Foxp3+CD4+T cells. eir abundance might be modu-
lated by co-inhibitory receptors. is might determine the ecacy of the
immune therapy as well as patient outcome.
Conclusion: e cellular origin of pro-tumorigenic IL-17A+Foxp3+CD4+T
cells is critical, as it could determine dierent therapeutic strategies to
contrast the cancer fostering activity. is may help to generate promising
immunotherapies for CRC patients.
Disclosure Statement: e authors declare no conict of interest.
972
Ecacy of Carboplatin and Cabazitaxel in Heavily Pretreated
Patients with Metastatic Castration-Resistant Prostate Cancer
Nadja Strewinsky1; Sergey A. Dyshlovoy1,2; Victor M. Schüttfort3;
Derya Tilki2,3; Su Jung Oh-Hohenhorst2,4; Markus Graefen3;
Carsten Bokemeyer1; Gunhild von Amsberg1,2
1University Medical Center Hamburg-Eppendorf, Hubertus Wald Tumorzentrum
– University Cancer Center Hamburg (UCCH), Department of Oncology,
Hematology and Bone Marrow Transplantation with Section Pneumology,
Hamburg, Deutschland
2University Medical Center Hamburg-Eppendorf, Martini-Klinik, Prostate Cancer
Center, Hamburg, Deutschland
3University Medical Center Hamburg-Eppendorf, Department of Urology,
Hamburg , Deutschland
4Centre de recherche du Centre hospitalier de l’Université de Montréal
(CRCHUM) et Institut du cancer de Montréal, Montréal, Kanada
Background: Increasing treatment pressure of mCRPC patients are likely
causative for the rising numbers of aggressive variants of prostate cancer
(AVPC) with visceral metastasis and neuroendocrine features. Compared
to CBZ monotherapy, cabazitaxel (CBZ) combined with carboplatin
(CARBO) has demonstrated improved ecacy in AVPC.
Methods: We retrospectively analysed mCRPC patients who received
CBZ plus CARBO therapy at the University Medical Center Hamburg-
Eppendorf between 12/2017-09/2020. Moreover, we investigated the in
vitro eects of CBZ+CARBO in human PCa cells exhibiting dierent lev-
els of resistance to taxanes as well as changes in cellular proteome.
Result: In total, 16 patients were eligible for analysis with a median age
of 63 years. At treatment initiation 75% had visceral metastases. On aver-
age, men had previously received 3.5 lines of treatment, including CBZ
monotherapy. A PSA decline ≥30% was seen in 44% of patients. Median
PFS was 4.5 months. Patients who completed all 6 cycles of CBZ+CARBO
achieved sustained disease stabilisation in 56% of cases. Despite prior
treatment with CBZ, 5 of the 11 pre-treated patients showed stable disease.
In vitro experiments revealed synergistic eects of CBZ+CARBO in
AR+ and AR- neuroendocrine PCa cells. Additive eects were detected
in AR- Du145 and PC3 cells, and in their docetaxel resistant (DR) sub-
lines. Remarkably, the latter showed increased sensitivity to CARBO.
Proteomics analyses of DR cells treated with either CBZ+CARBO or
CARBO alone revealed suppression of several drivers of epithelial-
mesenchymal transition and neuroendocrine dierentiation, such as
EGFR, STAT3 and Wnt/β-catenin signalling.
Discussion: Our patient’s data were in line with previous trials. Notably,
CBZ pre-treated patients responded to CBZ+CARBO and the in vitro data
suggest partial inversion of the AVPC phenotype.
Conclusion: Our data conrm ecacy of CBZ+CARBO combinational
therapy in AVPC. e synergistic eects as well as in increased sensitivity
to CARBO in DR cells may be related to a partial inversion of the AVPC
phenotype.
Disclosure Statement: e authors declare that there are conicts of interest. e
connections were submitted to the congress organizer KUKM GmbH and KUKM
can disclose them if needed.
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Oncol Res Treat 2022;45(suppl 1):7–284Abstracts 263
1026
Establishment of a living biobank of Pancreatic
Adenocarcinoma organoids to develop personalized
approaches
Christopher Neumann1; Marie Bossen1; Sandra Liebs2,3; Jana Ihlow4;
Georg Hilfenhaus1; Marcus Bahra5; Loredana Vecchione1;
Johann Pratschke6; Sebastian Stintzing1; Ulrich Keilholz2; Uwe Pelzer1
1Department of Internal Medicine, Division of Hematology, Oncology and
Tumorimmunology, Charité Campus Mitte, Charité - Universitätsmedizin Berlin,
Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin,
and Berlin Institute of Health, Berlin, Deutschland
2Charité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin,
corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin,
and Berlin Institute of Health, Berlin, Deutschland
3German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ),
Heidelberg, Deutschland
4Institute of Pathology, Charité Campus Mitte, Charité - Universitätsmedizin
Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu
Berlin, and Berlin Institute of Health, Berlin, Deutschland
5Center for oncological upper abdominal surgery and robotics, Hospital
Waldfriede, Berlin, Deutschland
6Department of Surgery, Charité Campus Mitte & Campus Virchow Klinikum,
Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität
Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin,
Deutschland
Introduction: Pancreatic adenocarcinoma is one of the most lethal types of
cancer and is progressively gaining attention since it is predicted to be the
second most common lethal cause of cancer by 2030. Recent approaches
have been made to explore the potential of patient-derived organoid
pharmacotyping as a possibility towards precision medicine. us, rst
correlations between the clinical response to therapy in patient-derived
organoids and PDX-models were made. is is a feasibility study of build-
ing up a biobank from various sample types of pancreatic cancer.
Methods: Resection samples and biopsies were minced, digested and l-
tered. Malignant cells of ascites were separated from lymphocytes through
magnetic labelling. Cells were than transferred into Matrigel and grown
in human complete feeding medium, including R-Spondin and WNT3a-
conditioned medium, 100 ng/ml Noggin, 100 ng/ml hFGF10 and 50 ng/
ml hEGF. e project is supported by the Charité Clinical Scientist pro-
gram and the “Berliner Krebsgesellscha e.v.”.
Results: Between Oct 2021 and Mar 2022 a total of 10 organoid cultures
were established from 26 pts, including tissue from surgical resections of
the primary tumor (5/10), biopsies of liver metastases (4/10) and ascites
(1/10). e total isolation rate was 69% (18/26) with an overall establish-
ment rate (min. 3 passages) of 38% (10/26).Histopathological characteris-
tics (HE-, Ki67-, TP53-staining) of the organoids proved to be consistent
with the tumor samples reecting high consistencies.
Conclusion: is work focused on the feasibility of building up a bio-
bank of pancreatic cancer organoids from various dierent sample types,
including resection samples, biopsies and ascites. In nearly 40% of the
samples, organoids were successfully established and used for further
functional analysis. e primary aim of this biobank being the exploration
of primary and secondary resistance pathways. Organoids will be exposed
to sequential cycles of chemotherapy (mFOLFIRINOX vs. Gemcitabin/
Paclitaxel) and resistance mechanisms will be identied on a proteomic
level.
Disclosure Statement: e authors declare no conict of interest.
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© 2022 S. Karger AG, Basel
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Autorenindex
A
A. Kestler, H. 131
Abbosh, C. 218
Abdullayev, N. 787
Abenhardt, W. 252
Abou Kors, T. 131
Abou-Madian, Ahmed Y. 522
Abramova, A. 740
Abramson, J. 968, 967
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Ackermann, U. 359
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Adams, Hans-Peter 902
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Aftimos, P. 504
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Agarwal, A. 208
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Aguilar-Cordova, E. 758
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Ahrens, M. 158
Aigner, C. 518
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Aker, S. 675
Akopov, A. 33
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Al Ahmar, E. 430
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Albers, P. 852
Albers-Leischner, C. 510
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Alberto, M. 388
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Alcaniz, J. 404
Aldisi, R. 379
Alekseev, B. 326, 952
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Aleric, I. 579, 760
Aleshchenko, E. 934
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Algül, H. 297, 950
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Alonso Gordoa, T. 308
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Ameline, B. 628
Amin, A. 534
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Ammerpohl, O. 131
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Anders, C. 608
Anderson Jr, Larry D. 150, 709, 560
André, F. 608
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Andreou, D. 804
Andrulat, A. 114
Angele, M. 219
Angeles, Arlou K. 482
Angelescu, K. 1032
Anjum, R. 989
Ankerst, D. 92
Ansmann, L. 161, 614, 706
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Antolín, S. 504
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Antonyan, I. 328
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Apostolova, P. 307
Appelgren, M. 269
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Araujo, Luiz H. 16
Aretz, S. 379
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Armstrong, A. 881
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Augustin, M. 128
Autengruber, A. 266
Avery, E. 414
Azhakesan, A. 143
Azria, D. 970, 946
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Bacher, R. 446
Bachmann, Hagen S 128
Backsch, C. 662
Badros, Ashraf Z. 534
Bady, E. 1029, 1054, 1031, 1053
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Bai, Y. 748
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Bald, T. 551
Baldus, C. 638, 679
Balermpas, P. 476
Balic, M. 66, 504
Balk, M. 261
Ballweg, A. 419
Balsen, Eva-M. 1023
Baltas, D. 513, 591
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Balzer, B. 390
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Bamberger, N. 398
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Banito, A. 749
Bankfalvi, A. 199
Bannert, H. 233
Banys-Paluchowski, M. 269, 676
Bar, J. 256
Baran, C. 458
Baranowsky, A. 120
Bardia, A. 936, 283
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Bargou, Ralf C. 419
Barker, Scott S. 255
Barone, F. 758
Barrett, J. Carl 911, 218
Barrios, C. 283
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Bartenstein, P. 613
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Bartzke, C. 638
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Oncol Res Treat 2022;45(suppl 1):7–284Author Index 265
Bashir, S. 325
Bast, C. 588
Basteck, S. 765
Basu, O. 673
Batenhorst, I. 297
Bauer, E. 502
Bauer, L. 522
Bauer, M. 198, 900
Bauer, S. 486
Bauer, T. 518
Bauerfeind, I. 114
Bauernfeind, Franz-G. 551
Bauersachs, R. 621
Bauerschmitz, G. 353
Baues, C. 339
Baumann, F. 321, 562, 773,
778, 20, 548, 570,
631, 647, 673, 727,
735, 767, 772
Baumann, K. 674
Baumann, M. 415
Baumann, S. 975
Baumgarten, P. 568
Baumhoer, D. 628
Baust, K. 934
Bayerlova, M. 815
Bazhin, A. 219
Beach, CL 287
Becher, B. 307
Beck, Eva M. 1024
Becker, G. 847
Becker, I. 476
Becker, Jan C 573
Becker, M. 209, 243
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Becker, N. 852
Becker, S. 299
Becker, S. 565, 580
Beckert, H. 518, 622, 416
Beckhove, P. 613
Beckinger, S. 490, 179
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Beckmann, M. 31
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Bednarsch, J. 174
Beer, K. 662, 680
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Behlendorf, T. 474, 869
Behr, Bj. 251
Behrens, B. 745
Behrens, F. 909
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Behzad, A. 720, 951
Beier, D. 779
Beier, F. 739
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Beitzen-Heineke, A. 731
Beksac, M. 150
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Belka, C. 359
Belleli, R. 33
Beller, R. 2, 1060
Bellet, M. 283
Belleville, E. 385
Belotte, J. 636
Beltzig, L. 43, 52, 53, 768
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Belz, H. 266
Ben Khaled, N. 425
Benary, M. 260
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Bengsch, F. 211
Benitez, D. 523, 788
Benndorf, M. 591
Benner, A. 852
Bennett, E. 33
Bennouna, J. 942
Bennstein, Sabrina B. 1060
Bens, M. 131
Benz, Stefan R. 1039
Benz-Rüd, I. 128
Bercker, S. 1023
Berdeja, J. 560, 709
Berg, J. 156
Berg, T. 211
Bergelt, C. 871, 976
Berger, K. 621, 779
Berger, Martin R. 368
Berger, W. 1045
Bergholz, A. 876
Bergmann, L. 152, 153, 158
Bergmann, M. 456
Beringer, A. 223
Berking, C. 456
Berlit, S. 522
Bernabe, R. 868
Berndt, U. 198
Berner, F. 551
Bernhardt, C. 135, 245
Bernhardt, K. 300
Berton, D. 990
Bertram, H. 532
Bertram, M. 519
Besse, B. 255
Best, J. 425
Bestvater, F. 749
Bethmann, D. 751
Bettinger, D. 425
Beutel, G. 1014
Beutel, Manfred E. 996, 997, 1057
Beutner, D. 63
Beyer, S. 118, 132, 571
Bhadri, V. 450
Bieback, K. 143
Bieber, B. 646, 513
Bielack, S. 628
Bierbaum, V. 515, 531
Bigot, P. 222
Bilsing, B. 615
Binninger, A. 259
Birkenfeld, F. 739
Birkl-Toeglhofer, Anna M. 404
Birkner, T. 799, 1039
Biro, D. 555
Bischof, G. 975, 1022
Bischo, C. 136, 974
Bischo, H. 868, 908, 413, 707
Bitter, E. 912
Bittner, Ann-K. 157
Bitzer, M. 335
Bjelic-Radisic, V. 1027
Blais, Edik M 1005, 1003
Blakely, C. 50
Blankart, K. 278
Blankenstein, T. 681
Blanksma, A. 706
Blasi, M. 413
Blau, W. 410
Blay, Jean-Y. 906, 916
Bleckmann, A. 345, 391, 808, 815
Bleich, C. 137
Bleif, M. 847
Blessin, Niclas C. 1029, 1031, 1053, 1054
Bleumer, T. 1049, 1052
Bloch, W. 136, 575, 659, 974, 987
Bloedt, S. 914
Blohmer, Jens-U. 269, 504, 1027, 676
Blome, C. 905
Blum, Steven I. 920
Bobbili, D. 379
Bobeth, C. 531
Bochtler, T. 223
Bockmühl, U. 63
Boddu, V. 603, 1042
Bode-Greuel, K. 204
Bögemann, M. 67, 82, 158, 253,
266, 326, 898
Böger, D. 430
Bohle, R. 556
Böhmerle, W. 159, 1049, 1052
Bojarski, C. 855
Bokemeyer, C. 972, 976, 137, 312,
731, 895, 616
Bokemeyer, F. 137
Boklage, S. 1050
Bolenz, C. 79
Boleti, E. 158
Bollschweiler, E. 767
Bolm, L. 1009
Boltenhagen, Ursula. 692, 720, 951, 1067
Bölükbas, S. 433, 606
Bonci, Eduard-A. 269
Bondarenko, I. 908, 1036, 33
Bondarets, V. 929
Boni, V. 730, 990, 1055
Böning, G. 943
Boos, J. 673
Boppudi, Sanga M. 181
Borchardt, J. 306
Borchert, S. 622, 199, 416, 518
Borchmann, P. 339, 610
Borde, J. 361
Borges, V. 309
Borghaei, H. 920
Borghesi, G. 327
Borgmann, S. 1014
Borgovan, T. 989
Bornhäuser, M. 134, 804, 874
Bosancu, I. 40
Bösch, F. 219
Bösche, J. 90
Bossart, M. 341
Bossen, M. 1026
Bossert, J. 547, 1067
Boston, S. 608
Boström, Jan P. 783
Boström, K. 634
Bothur, S. 724
Bougatf, N. 191
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Oncol Res Treat 2022;45(suppl 1):7–284 Author Index266
Bourgeois, M. 739
Boz, S. 159
Bozorgmehr, F. 47, 244, 482, 500, 707
Bozzetti, T. 405
Bradley, William H. 674
Brähler, E. 996, 997
Brahmer, Julie R. 920
Braicu, Elena I. 291, 302
Branchi, F. 855
Brand, H. 722, 976
Brand, T. 278
Brandl, A. 524
Brandstetter Vilar, J. 768
Brandts, C. 510
Brauer, N. 625
Braulke, F. 866, 1006
Braumann, C. 814
Braun, M. 306, 114
Braun, R. 1009
Braun, T. 954
Brauner, R. 881
Braverman, J. 968
Bray, V. 256
Brcic, L. 416, 622
Breckner, A. 204
Breidenbach, C. 127
Breitenstein, U. 66
Brenner, H. 532, 358
Brenner, W. 756
Breuing, J. 914
Breyer, J. 79
Brichard, B. 450
Briers, E. 970, 946
Broadhurst, H. 911
Brockmeyer, P. 329
Broge, B. 204
Bronsert, P. 1009
Brors, B. 829
Brossart, P. 995, 551, 921, 262
Brown, Jennifer R. 349, 374, 411
Brown, J. 730, 1055
Bruch, D. 167
Brück, V. 522
Brückl, N. 94
Brückl, W. 40, 94, 280, 391, 777
Brufsky, A. 936
Brümmendorf, Tim H. 739
Bruners, P. 119
Brüning, F. 128
Brunner, C. 131
Brunner, J. 708
Brunner, M. 761
Brunner, T. 59, 74, 476, 714, 784,
786, 787, 789
Bruns, C. 502, 649, 810, 428
Bruns, R. 370, 840
Bryn, G. 239
Brzezicha, B. 524, 681
Brzoska, P. 835, 1068
Buchele, C. 578
Büchele, T. 504, 1027
Buchhold, B. 46
Buchholz, M. 814
Buchholz, T. 21, 22
Buchkremer, J. 855
Büchler, C. 347
Buchmann, J. 751
Büchner-Steudel, P. 198
Buckstein, R. 281, 282
Budach, V. 410, 884
Budach, W. 476
Buettner, F. 620
Buettner, R. 817
Bühler, H. 783
Bühn, S. 914
Bultjinck, R. 946
Büntemeyer, Tjark-O. 493
Büntzel, J. 430, 453, 686, 63
Büntzel, J. 465, 467, 682
Büntzel, Sören K. 682
Burdach, S. 628
Burderath, P. 199
Burger, M. 79
Bürger, T. 566
Burges, Alexander. 118, 132, 571
Burgués, Juan Miguel B. 891
Burke, John M. 891
Bürkel, F. 512
Bürkle, D. 103
Burn, Timothy C. 335
Burock, Susen 605
Bürrig, Karl-F. 751
Bürtin, F. 535
Busch, Chia-J. 63
Busch, H. 1042
Busch, U. 74
Büsch, C. 1065
Bushong, J. 920
Busse, A. 681
Büttner, R. 446, 510, 810, 912
Büttner, T. 79
Buziba, N. 716
Byers, L. 911
Byl, A. 398
Byrd, John C. 411
Byrne, J. 991
Bytyqi, F. 275
C
Cabanillas, M. 277
Cabuk, C. 40
Çakmak-Görür, N. 681
Calaminus, G. 934
Callenoni, M. 309
Calvert, Paula M. 674
Cameron, S. 293
Campbell, P. 414
Campbell, T. 560, 208, 709
Campillo, M. 669
Cannell, P. 956
Carbone, David P. 942
Cardoso, F. 870
Carey, L. 936
Carl, Ernst-G. 914
Carles, J. 327
Carmelo, V. 877
Carmen, L. 267
Caro, Reyes B. 920
Carr, P. 358
Carver, J. 989
Casper, J. 82
Castellano, D. 158
Castillo-Binder, P. 381
Cavailles, V. 828
Cavo, M. 560, 709, 208
Cedzich, C. 275
Chaft, J. 50
Chalabi, N. 223
Chalas, S. 655
Chalopin, C. 689
Chamorro-Vina, C. 1060
Chan, A. 553
Chan, Wai Y. 956
Chanan-Khan, A. 411
Chang, Ching-W. 283
Chang-Claude, J. 970, 358, 946
Chao, Y. 1064
Charalambous, N. 593
Chauchet, A. 891
Cheah, Chan Y. 516, 349
Chekerov, R. 302
Chella, A. 33
Chemnitz, J. 486
Chen, J. 1036
Chen, M. 534
Chen, Njin-Z. 119
Chen, Y. 908
Chen, Y. 817
Cheng, S. 956
Cheng, Y. 840, 942
Cheung, Matthew C. 891
Chiabudini, M. 135, 246
Chiocca, E. Antonio 758
Cho, Byoung C. 16
Chodan, W. 642
Chouaid, C. 868, 256
Choudhury, A. 970, 946
Choueiri, Toni K 151
Christmann, J. 788
Christmann, M. 43, 768
Christoph, B. 515
Christoph, Daniel C. 128, 416, 135,
256, 433, 606
Christopoulos, P. 47, 135, 244, 482,
500, 707, 413
Chugh, P. 911, 908
Chung, I. 413
Cicchetti, A. 946
Cidre-Aranaz, F. 749
Ciruelos, E. 210
Ciuleanu, Tudor-E. 920, 942
Claßen, Annika Y. 1041
Claus, R. 669
Clausen, S. 522
Clement, Joachim H. 323
Clements, A. 636
Clezardin, P. 120
Co, M. 956
Cobo-Dols, M. 942
Coelho, R. 640
Cofre, A. 453
Cohen, Johnathon B. 516
Coleman, Robert L. 1050
Collaud, S. 450
Combs, Stephanie E. 359
Concalves, A. 504
Conev, Nikolay V 908
Conrad, T. 209, 243, 404
Conradi, Lena-. 1, 292, 808, 815, 583
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Oncol Res Treat 2022;45(suppl 1):7–284Author Index 267
Conrads, K. 583
Cook, G. 534
Cook, N. 223
Coombs, Catherine C. 349, 516
Cords, H. 312, 418
Corradini, S. 118, 571
Corre, R. 989
Cortes, J. 936
Cortesi, F. 933
Cosenza, M. 586
Coto-Llerena, M. 104, 89
Coudert, B. 553
Coupland, S. 853
Cove-Smith, L. 868
Coym, A. 312
Cramer, T. 627
Crawford, D. 952
Creutzig, U. 673
Crispin, A. 947, 955, 1016
Croner, R. S. 604, 736, 742, 759, 781, 809
Crotta, A. 968, 967
Croydon, E. 1064
Crysandt, M. 486
Cubillo Gracián, A. 714
Cui, K. 950
Culmsee, C. 754
Cumin, C. 620
Cyprova, S. 450
Czauderna, C. 443
Czogalla, B. 132, 571
D
D’Angelo, Sandra P. 690, 700
Dacic, S. 50
Dadras, M. 251
Däggelmann, J. 136, 575, 659, 974, 987
Dahl, E. 174
Dahlmann, M. 404, 524, 605
Daley, W. 1036
Dalferth, R. 169, 172
Daltrozzo, T. 297
Dalvi, T. 908
Dambacher, S. 252
Damber, Jan-E. 328
Daniel, M. 572
Dannecker, C. 828
Darr, C. 82, 152
Darsow, M. 429
Darwich, A. 12
Das, P. 971
Däster, S. 89
Daunke, T. 490, 179
David, F. 379
Davids, Matthew S. 349
Davies, Faith E. 691
Dayan, D. 656, 658
D‘Cruz, C. 608
de Boer, C. 866, 1071, 1075
de Boniface, J. 269
De Braud, Filippo G. 255
De Geest, S. 180
de la Mora Jimenez, E. 942
De la Serna, J. 414
De Lazzari, N. 20, 562
de Oliveira, T. 808
De Oliveira, T. 583
De Ruysscher, D. 946, 970
de Schultz, M. 874
De Toni, E. 425
de Wit, M. 171, 945
DeArbeloa, P. 1005, 1003
Debatin, Nicolaus F. 1029, 1054
Debus, D. 73, 544
Debus, Jürgen P. 36, 47, 191, 234, 244,
360, 500, 578, 851, 852
Deckbar, D. 158
Decker, T. 246, 340
Degenhardt, T. 298
Degenkolbe, E. 898
DeGregorio, A. 1059
Deichmann, S. 1009
Deis, N. 888
Delebinski, L. 1015
Delforge, M. 709
Delker, A. 943
Delmastro, N. 171
Delmonte, A. 868
Demmler, R. 864
Denkert, C. 504, 1027, 114
Depenbusch, J. 197
Derani, H. 880
Dernoscheg, Marie-T.e 544
Deryal, M. 302
Desai, J. 690, 700
Dey, A. 218
Dhanasiri, S. 691
Dhar, A. 989
Di Bartolomeo, M. 1064
Di Micco, A. 534
di Micco, R. 269
Di Pace, B. 989
Di Pietro, A. 151
Diekmann, A. 161
Dielmann, A. 260, 563
Dienstmann, R. 906, 916
Dieras, V. 936, 283
Dierkes, S. 754
Diers, J. 396
Diestelhorst, A. 499
Dietlein, M. 339, 446
Dietrich, D. 663
Dietrich, S. 891
Dietz, A. 262, 63
Dietz, T. 844
Dietzel, F. 745
Diez-Campelo, M. 281, 282
Dimopoulos, M. 150, 971
DiNardo, C. 956
Dinges, S. 522
Dinkel, A. 297, 92, 359
Dintner, S. 669
Dippmann, C. 445, 680
Dirksen, U. 450, 647, 673, 749, 765
Disler, M. 640
Distel, L. 607, 512
Distelrath, A. 66
Dittmar, G. 605
Dobler, F. 828
Doege, D. 532
Doehn, C. 780, 794, 795, 898
Doescher, J. 131
Döhner, H. 287
Dolan, S. 414
Doleschall, Anna D. 1041
Dommerich, S. 262
Donath, S. 34, 78, 101, 227, 747, 757,
776, 584
Donaubauer, Anna-J. 476
Doppler, A. 456
Dörenberg, J. 174
Dörfel, S. 280, 245, 259, 869
Döring, K. 713, 776
Döring, S. 673
Dornstauder, E. 881
Dörr-Harim, C. 165
Dørumn, A. 674
Dostalek, L. 269
Doyle, C. 309
Dräger, Desiree L. 21, 22, 23
Drageset Haakensen, V. 256
Dreimann, M. 895
Dreismann, L. 26
Dressler, J. 146
Dreyling, M. 516
Drilon, Alexander E. 255, 277
Dröge, Leif H. 34, 78, 101, 227,
713, 747, 757,
776, 1077, 584
Dröge, P. 515, 531, 934
Droste, A. 451, 473, 471
Drzezga, A. 446
Duan, T. 730
Dubecz, A. 40
Ducreux, M. 32
Dudas, C. 485
Dueñas, N. 379
Dum, D. 1053
Dummer, R. 73
Duran Cortes, M. 171
Duran-Pacheco, G. 223
Dürsch, H. 1067
Dürst, M. 445, 662, 680
Dusel, J. 1018
Duska, L. 730
Dutailly, P. 222
Duyster, J. 307, 1042
Dwinger, S. 731
Dysarz, J. 302
Dyshlovoy, Sergey A. 972
Dytfeld, D. 971
E
(OSHO), East German Study
Group of Hematology
and Oncology 228, 229
Ebeling, M. 959
Eberhardt, Ina M. 529
Eberhardt, Wilfried Ernst E. 280, 135
Eberl, I. 49
Eberle, A. 532
Eberle, M. 669
Ebert, M. 1039
Eccles, L. 920
Eckert, K. 673
Eckford, R. 415
Eckstein, M. 79, 261, 458, 476
Edelmann, F. 159
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Oncol Res Treat 2022;45(suppl 1):7–284 Author Index268
Edelmann, M. 808, 583
Egerer, G. 486
Egger, E. 302
Eggers, E. 245
Eggert, A. 201
Egyed, M. 166
Ehlert, S. 198
Ehmann, M. 522
Ehneß, R. 898
Ehrenthal, J. 360
Ehret, F. 847, 884
Ehrmann, J. 648
Eich, Hans T. 268, 573, 450
Eichbaum, M. 302
Eichenauer, D. 339
Eichenauer, Rolf H. 780, 794, 795
Eichhorn, A. 721, 506
Eichhorn, F. 482, 707
Eichhorn, Martin E. 413
Eichhorst, B. 374
Eichkorn, T. 36, 47, 244, 500, 578, 851
Eichler, MSc., M. 804, 702
Eickho, R. 85
Eidt, S. 94
Eifert, T. 323
Eigentler, T. 267
Einsele, H. 560, 709
Einspieler, I. 813
Eisert, A. 912
Ek, T. 450
Ekanem, Ima-O. 823
El Shae, R. 78, 101, 191, 227,
244, 360, 500,
747, 757, 47
Eliason, L. 991
Ellard, Susan L. 990
Ellenrieder, V. 293
Ellinger, J. 79, 551
Elmers, S. 826
El-Rajab, I. 617, 741
Elshiaty, M. 482
Elter, T. 980
Emmler, A. 352
Emons, G. 594
Endres, M. 159
Engel, C. 361
Engel, E. 246
Engel, J. 311, 441, 539, 114
Engeland, K. 381
Engels, N. 1
Engert, A. 339
Englmeier, F. 391
Erb, C. 238
Erben, P. 79
Erber, R. 31
Erbersdobler, A. 880
Erbes, T. 586
Ercan, C. 89, 104
Ercan, H. 562
Erdem, M. 627
Erdmann, G. 325
Erickson, N. 298
Ernst, C. 361
Ernst, J. 292
Ernst, J. 5, 857
Ernst, K. 737
Ernst, M. 996, 997
Ernst, P, 323
Ernst, T, 100, 430, 961, 1056
Ernstmann, N, 161
Erschig, R. 673
Eschbach, J. 810
Eschmann, S. 1066
Escriu, C. 50
Escudier, B. 158
Esposito, I. 745
Esser, K. 405
Esser, P. 5, 610, 616
Eto, M. 308
Ettl, T. 111
Ettrich, Thomas J. 425
Evans, B. 1044
Everest-Dass, A. 620
Evers, G. 345
Evert, K. 111
Evripidou, G. 788
Exner, S. 684
Exner, S. 909
Eyl, Ruth E. 358
Eymard, Jean-C. 222
Eyre, Toby A. 349, 516
Ezić, J. 131
F
F.E. Barth, T. 131
Faber, J. 997
Fabre, S. 281, 282
Faehling, M. 1066
Fähndrich, S. 204
Failing, T. 78
Faitg, T. 690, 700
Faivre-Finn, C. 868
Fakhri, B. 349, 516
Falk, M. 554
Falkenthal, J. 624
Fallscheer, S. 1066
Faltus, T. 198
Fan, S. 583
Fang, N. 817
Farcy-Jacquet, Marie-P. 970
Farwick, N. 31
Fasching, Peter A. 31, 504, 1027, 676
Faulhaber, Eva-M. 512
Faust, E. 181
Fear, S. 916
Feder, I. 523, 788
Fedier, A. 640
Feeney, K. 942
Fehlauer, F. 909
Fehm, T. 340, 380, 405, 590,
740, 745, 748, 785,
954, 1059, 676
Feil, C. 368
Felberbaum, R. 656, 658
Feldmann, G. 995, 921
Feliciano, Joana G 877
Felip, E 33, 370, 989
Felser, S 228, 229
Fenaux, P. 281, 282
Feng, W. 309
Fennell, Jamina T. 513
Fenske, T. 516
Ferrajoli, A. 374
Ferrant, E. 166
Ferraro, F. 931
Ferreira, Cesaltina L. 716
Fetzner, Ulrich K. 767
Feuchter, J. 716
Feuchtinger, T. 356
Feufel, M. 397, 889
Feyerabend, S. 328, 327
Fichte, S. 847
Ficker, J. 94, 777
Fiebig, C. 233
Fiedler, R. 472
Field, J.K. 256
Fiesel, P. 829
Fietkau, R. 254, 261, 476, 512, 256
Filippi, A.R. 256
Filipski, K. 567
Finas, D. 1004
Fink, A. 954, 1059
Finke, G. 1030
Finke, I. 675
Finkelmeier, F. 425, 443
Finn, Richard S. 32
Finster, Agnes M.E. 829
Fisch, D. 707
Fischer, J. 78
Fischer, Laura A. 34, 101, 227,
747, 757, 776
Fischer, R. 912
Fisseler-Eckho, A. 181
Fitilidis, K. 462
Fizazi, K. 326, 327, 328, 952
Flach, M. 555
Flachs-Nóbrega, S. 529
Flatz, L. 551
Fleckenstein, K. 522
Fleischmann, B. 869
Fleitz, A. 135, 280, 391
Fleming, Evelyn. L. 636
Fleuter, C. 605
Flier, A. 99
Flinn, I. 516
Flock, F. 656, 658
Flörcken, A. 82, 152, 158
Fluck, M. 73
Flügen, G. 744
Fogliatto, Laura M. 166
Fokas, E. 1039
Folchini, Decio M. 233
Foller, S. 100
Follmann, M. 914
Follows, G. 166
Fong Ng, T. 956
Forget, F. 674
Foroutanpour, K. 868
Forrester, T. 436
Forschner, A. 73
Forstbauer, H. 103
Forster, A. 368
Förster, S. 1039
Forstner, A. 379
Fragoulis, A. 627
Frank, T. 297, 359
Franke, Fabio A. 1074
Franke, K. 612
Franke, s. 59
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Oncol Res Treat 2022;45(suppl 1):7–284Author Index 269
Franken, A. 745, 590, 380, 740
Freiberg-Richter, J. 211
Freidank, A. 754
Freitag, D. 568
French, P. 277
Frenkl, T. 337
Frenz, S. 914
Frerichs, W. 312, 418, 871
Freudlsperger, C. 360
Frey, B. 476
Freyer, B. 905
Freyer-Adam, J. 46, 975, 1022
Friedberg, JonathanW. 891
Friederich, Hans-C. 324, 360
Friedl, Thomas W. P. 340, 954, 1059,
676, 380
Friedman, E. 361
Friedrich, M. 616, 699, 1030
Friedrich, S. 1061
Fries, J. 661, 701, 698
Fritsch, R. 103
Fröhlich, K. 586
Fröhlich, S. 269
Frohwitter, G. 458
Frontado Grae, Freddy J. 995
Fruehauf, S. 245
Fruendt, T. 425
Fuchs, M. 339
Fuentes Pradera, J. 674
Fuhr, R. 494
Funk, C. 749
Funke-Lorenz, C. 307
Furlanetto, J. 504
Furman, Richard R. 411
Fürweger, C. 884, 847
G
Gaedcke, J. 1
Gagliani, N. 933
Gainey, M. 591
Gaipl, U. 476
Gaisa, N. 174
Gaisser, A. 415
Gaissmaier, L. 482
Gajate, P. 222
Gajda, Mieczyslaw R. 662
Galle, Peter R. 32, 211
Gallwas, J. 353, 588
Galonska, L. 574
Galuba, J. 606
Gambara, G. 524
Ganguli, A. 881
Ganly, Peter S. 374
Garassino, Marina C. 370, 868, 908, 256
García, Marc D. 1064
Garcia-Manero, G. 281, 282
García-Márquez, M. 502, 649, 428
Garcia-Saenz, Jose A. 436
Garlipp, B. 736, 738
Garon, Edward B 16
Garrido, F. 828
Garrido, P. 256
Garside, J. 1050
Gärtner, B. 975
Gasche, N. 1037
Gaser, D. 356
Gasimli, K. 565, 580
Gasiorowski, R. 956
Gasparri, Maria L. 269
Gasparro, D. 328
Gaß, P. 31
Gaßler, N. 662
Gaßmann, Karl-G. 233
Gastinger, I. 736, 738, 742
Gathof, B. 502
Gauler, T. 262, 63
Gauß, G. 2, 673, 1060
Gautschi, O. 255
Gawish, A. 784, 786, 789, 74
Gay, C. 911
Geater, Sarayut L. 16
Gehlhaar, A. 167
Geisen, S. 53
Geissler, J. 906, 916
Gelderblom, H. 450
Gemoll, T. 1042
Gengenbacher, L. 73
Gentilini, O. 269
George, Julie 502
Geppert, Carol I 864
Gerber, J. 302
Gerger, A. 103
Gerken, M. 355, 441, 462, 903,
492, 452, 515, 531
Gerlach, R. 621
Germer, Christoph-T. 396
Germing, U. 281, 282
Gerson, James N. 516, 349
Gerthofer, V. 611
Geue, K. 699
Geyer, S. 102
Ghadimi, M. 1, 292, 593, 594,
808, 583, 529
Ghadjar, P. 591
Ghamande, S. 730
Ghasemi, D. 737
Ghatage, P. 730
Ghataorhe, P. 991
Ghia, P. 166, 349, 411, 414, 516
Gianni, L. 936
Giannou, A. 933
Gierke, B. 590
Giese, N. 1002
Gieseler, F. 603, 1042
Giesemann, N. 874
Giesen, N. 1041
Giesler, S. 307
Giessen-Jung, C. 1014
Giladi, M. 460
Gilbert, L. 730, 990, 1055
Gildehaus, Franz-J. 943
Gillespie-Twardy, A. 374
Giordano, Frank A. 921
Girard, N. 256
Gires, O. 1042
Gitlitz, B. 33
Gkika, E. 714
Glade, J. 413
Glajzer, J. 458, 493
Glas, M. 254
Glaser, M. 454
Glaser, M. 912
Glaspy, J. 1036
Glaß, B. 968, 967
Glien, A. 474
Glowik, R. 291
Glowka, T. 995
Gnahatin, F. 823
Gockel, I. 399, 643, 689, 697
Goebel, Anna-M. 673
Goebell, Peter J. 67, 128, 153, 898
Goedicke-Fritz, S. 426
Goeppner, D. 73
Goerling, U. 857
Goertz, S. 625
Goetz, C. 739
Goetze, Thorsten O. 85, 357
Gökkurt, E. 357
Golan, T. 950
Gold, J. 726
Goldbrunner, R. 254
Goldhardt, T. 808, 583
Golding, S. 223
Goldman, Jonathan W 908
Goldschmidt, H. 630, 709, 208
Golla, A. 499
Göllner, S. 403
Gonçalves, M. 86
Gonzalez-Carmona, Maria A. 425, 921, 995
González-Martín, A. 654, 674
Göppner, D. 267
Gorantla, H. 603
Gorantla, Sivahari P. 1042
Görner, M. 262
Gostian, Antoniu-.261, 432, 476
Goto, K. 255
Götte, M. 2, 20, 617, 625, 647,
673, 741, 765, 1060, 356
Götz, M. 276
Götze, L. 200
Götze, T. 989
Grabbert, M. 327
Grabellus, F. 433
Grabher, P. 984
Grabowski, J. 654, 674, 636
Grabowski, M. 809
Grade, M. 1
Graefen, M. 972, 1031
Graf, K. 753
Graf, M. 441
Graf, S. 233
Grah, C. 135, 964
Grammatikopoulou, T. 866, 1075,
1075, 1073
Grapp, M. 324
Gratzke, C. 327, 591, 881, 359
Gravis, G. 158
Gravis-Mescam, G. 151
Gray, Heidi. J. 636
Grecea, D. 436
Gren, K. 655
Grehn, C. 40
Greif, P. 537, 555
Greil, R. 339, 891, 103
Greimelmaier, K. 622
Greiner, V. 134
Greiner, W. 961, 1056
Greiß, F. 159, 791
Greve, J. 131
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Oncol Res Treat 2022;45(suppl 1):7–284 Author Index270
Greve, M. 594
Gridelli, C. 989
Griesel, M. 716
Griesinger, F. 50, 135, 280, 370,
391, 694, 706, 712
Griewatz, J. 720
Grith, A. 758
Grillenberger, A. 783
Grimm, Marc-O. 128, 151, 158, 266
Grimmelmann, I. 267
Grimmig, T. 385
Gröger, C. 146
Groh, S. 22, 21
Grohé, C. 1007
Gröhnke, S. 826
Gröschel, A. 135
Grosicki, S. 971
Groß, J. 299, 102
Große Lackmann, K. 721, 506
Große-Thie, C. 228, 229
Gross-Goupil, M. 158
Großkinsky, U. 296
Groß-Langenho, M. 881
Groß-Opho-M., C. 980
Grosu, Anca-L. 140, 454, 460, 513,
591, 646, 714
Grote, L. 150
Groth, A. 135, 280
Groth, J. 410
Grove, C. 956
Grüllich, C. 67
Grün, J. 229
Gründker, C. 353, 588
Grundmann, H. 405
Grundmann, N. 618
Grundtner, P. 261
Grunert, C. 681
Grunert, M. 959
Grünewald, Thomas G.P. 749
Grünwald, V. 67, 82, 128, 152,
153, 266, 308, 410,
507, 898, 486
Grützmann, R.t 761
gryc, t.s 40
Gschwend, J. 945, 1024, 92, 359,
852, 929
Guder, W. 765
Guhlich, M. 34, 78, 101, 227, 292,
713, 747, 757, 776, 584
Gül-Klein, S. 524
Gumpp, J. 492
Günster, C. 515, 531
Günther, M. 635
Günther-Gunkel, M. 177
Guntinas-Lichius, O. 262, 430, 445
Guo, S. 968
Gupta, D. 654, 674
Gupta, Ravi G. 920
Gürgen, D. 201, 209
Gust, R. 984, 983
Guth, D. 66
Gutiérrez-Enríquez, S. 946
Gutsche, K. 63
Gütz, S. 265
Gutzmer, R. 267, 73
Guyot, M. 792
Guzik, Brian W 758
H
Ha, X. 282
Haag, Georg M. 1040
Haanen, John B.A.G. 690, 700, 158
Haas, B. 52
Haas, D. 785
Haas, P. 705, 717
Häberle, L. 31
Habermann, Felix-Nikolai Oschinka J.
78, 227, 747
Habibzade, T. 85, 357
Hachenberg, J. 629
Hackenberg, S. 739
Hackert, T. 1002
Hackl, M. 198
Häckl, D. 612
Hackshaw, A. 916, 906
Hadaschik, B. 507, 852
Haferkamp, S. 307, 73
Hage, Anna M. 127, 572
Hagemann, C. 485
Hager, T. 416
Hahlweg, P. 312, 418, 626
Hahn, D. 63
Hahn, L. 118
Hahn, M. 735
Hahn, S. 260, 897
Hahne, S. 912
Hahnen, E. 361, 663
Haidenberger, A. 884, 847
Hajduk, E. 793
Hakenberg, O. 21, 22, 23, 880
Hakimhashemi, A. 618
Halfter, K. 311, 539
Halle, L. 454
Hallek, M. 711, 980
Haller, K. 976
Halloul, Z. 609
Hallsson, Lára R. 1016, 947, 955, 1032
Hamacher, R. 486
Hamberg, P. 222
Hamilton, E. 608, 636
Hammel, P. 950
Hammerer, P. 29
Hämmerl, L. 716
Hammling, M. 562
Han, Xi. 990
Handmann, C. 778
Hanenberg, H. 561, 1060
Hanf, V. 751
Hanker, L. 730, 1055
Hansel, A. 445, 680
Hanses, F. 1014
Hanusch, C. 504, 1027
Hapgood, G. 891
Hapke, G. 262
Harbeck, N. 66, 210, 246,
297, 298, 870,
877, 114, 359
Harde, J. 128
Hardes, J. 450
Hardesty, Melissa. M. 636
Harnischfeger, N. 976
Härter, M. 312
Hartkopf, A. 340, 676
Hartmann, Amelie. 679
Hartmann, A. 31, 79, 153, 158,
476, 556
Hartmann, J.T. 410
Hartmann, M. 100
Hartmann, S. 269
Hartmann, W. 345, 450, 749
Hasanov, Mir F. 341
Hasenburg, A. 451, 471, 473, 756
Hassanin, E. 379
Hassel, Jessica C. 73
Hasselmann, K. 537, 555, 779
Hattingen, E. 567
Hattingen, L. 1001
Hatzipanagiotou, Maria E. 611, 903
Hau, P. 613
Haubrock, M. 1
Hauck, T. 607
Hauke, J. 663
Hauprich, J. 914
Hauptmann, M. 269
Hauser, P. 450
Haussmann, A. 197
Hautmann, M. 111, 146, 262, 476
Haveman, L. 450
Haybaeck, J. 404
He, J. 50
He, S. 1002
He, W. 991
He, Y. 53
Headley, D. 436
Hebbel, H. 169, 172
Hecht, G. 354
Hecht, M. 261, 476, 512
Heckelmann, B. 1009
Heesen, P. 450
Heeter, P. 1045
Hege, K. 709
Hegedüs, B. 416
Hegener, P. 429
Heger, T. 946
Hegewisch-Becker, S. 259, 867, 103
Hegg, R. 436
Heibges, M. 397
Heidegger, H. 828
Heidel, Florian H. 323
Heidenreich, A. 661, 698, 701, 708,
711, 715, 980
Heidt, V. 519, 523
Heij, L. 174
Heiland, Dieter H. 140
Heimbach, D. 900
Heimes, Anne-S. 756
Heine, A. 551
Heine, R. 547, 692
Heinemann, V. 297, 537, 555, 359
Heinrich, K. 537, 555
Heinz, J. 593
Heinze, M. 167
Heinzelbecker, J. 556
Heinzelmann, F. 1066
Heinzelmann, J. 853
Heinzelmann-Schwarz, Viola 640, 620
Held, T. 47, 244, 360, 578
Heldmaier, W. 721
Hellmann, M. 218
Hellmis, E. 152
Helmbold, I. 946, 970
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Oncol Res Treat 2022;45(suppl 1):7–284Author Index 271
Helweg, M. 679
Hempel, E. 780, 794, 795
Hempel, S. 102
Hengstler, Jan G. 756
Hennig, A. 445
Henrichs, V. 238
Henrique, R. 556
Henschke, S. 370
Hense, J. 20
Henssen, Anton G. 201
Hentschel, L. 134, 635, 702, 804, 486
Henze, L. 1041
Herbaux, C. 891
Herber, M. 267
Herbolsheimer, P. 608
Herbst, R. 267, 410
Herden, J. 661
Herfarth, K. 36, 47, 244
Herhaus, P. 357
Hering-Schubert, C. 211, 103
Herishanu, Y. 166
Herkommer, K. 92, 359, 852
Hermelink, K. 297, 298, 359
Hermes-Moll, K. 519
Hernáiz Driever, P. 673
Hernandez, S. 32
Hernandez-Ilizaliturri, F. 967
Herold, T. 792
Herold, T. 537, 555
Herrmann, M. 864
Herrmann, T. 204
Herschbach, P. 359
Hertel, H. 601, 1015
Hertel, K. 902
Hertenstein, B. 339, 410
Herth, Felix J.F. 413, 482
Hess, Gabriel F. 89, 104
Hess, J. 646
Hester, A. 571
Hettler, M. 292
Heuer, A. 895
Heumann, P. 970
Heuser, C. 161
Heußel, Claus P. 86
Heußner, P. 359
Heydenreich, M. 55, 230, 231, 232
Heyder, U. 547
Heymanns, J. 519
Hietanen, S. 674
Higgins, K. 411
Hilfenhaus, G. 1026
Hilger, C. 397, 889
Hille, A. 101, 227, 757, 776
Hillebrand, Larissa E. 211
Hillemanns, P. 601, 629, 1015, 102
Hillmen, P. 374, 411
Hilser, T. 82, 153, 507
Himmelsbach, V. 425, 443
Hinke, A. 152, 476
Hinkel, A. 82
Hinz, A. 997
Hinz, N. 120
Hipper, A. 135, 280
Hirche, C. 612
Hirschmiller, J. 996
Hoang, B. 341
Hochhaus, A. 100, 323
Hochhauser, D. 950
Hochmair, Maximilian J 908
Höckel, M. 655
Hoechstetter, M. 252
Hoefert, S. 352
Hoegen, P. 578, 851
Hoeller, C. 73
Hoelscher, Arnulf H 767
Hoeltgen, L. 851
Höer, A. 862
Hof, A. 245
Höken, N. 788
Hoknecht, P. 1047
Homann, A. 662
Homann, J. 201, 209, 243, 404, 524
Homann, J. 456
Homann, M. 149
Homann, O. 157, 676
Homann, S. 947, 955, 1016
Homeister, M. 358
Hofheinz, Ralf-D. 1039
Hofmann, Hans-S. 462
Hofmann, Wolf P. 211
Hofmann, Wolf-K.n 12
Hoglander, E. 223
Hohenberger, P. 804
Höhn, P. 814
Hoier, D. 980
Holch, J. 537
Holländer, H. 298
Holland-Letz, T. 36
Hollburg, W. 267
Holleczek, B. 532
Hollnberger, F. 548
Holm, Per S. 1024, 929
Holmberg, C. 876
Hölters, S. 128, 556
Hölting, Tilman L. B. 749
Holtmann, L. 945
Holze, M. 165
Hölzel, M. 79, 551
Hölzle, F. 739
Homayounfar, K. 815
Honisch, E. 740, 785, 745, 561
Honselmann, K. 1009
Höpfner, F. 642
Höpken, Uta E. 296
Horch, Raymund E. 607
Horenkamp-Sonntag, D. 934
Hori, M. 971
Hörmann, N. 984
Horn, Lars-C. 190
Horn, L. 462
Horn, M. 120
Horneber, M. 951, 720
Hornemann, B. 134, 804, 857
Hörner-Rieber, J. 234, 360, 578, 851
Hortobagyi, G. 309
Hotta, K. 908
Hsia, Te-C. 840
Hsu, Chen-J. 323
Hu, N. 942
Huang, J. 374
Huang, L. 709, 208
Huang, Yen-L. 620
Hübbers, Christian U. 446
Hube-Magg, C. 1054, 1029, 1031, 1053
Huber, D. 611
Huber, G. 321
Huber, N. 323
Huber, S. 933
Hübner, Christian A. 323
Hübner, G. 103
Hübner, G. 499
Hübner, J. 686
Hucke, N. 252
Huebner, H. 31
Huebner, J. 100, 453
Huenniger, D. 639
Huerta, M. 715, 661, 708
Huesmann, S. 954
Hughes, C. 281, 282
Hühnchen, P. 159
Hultcrantz, M. 991
Hummel, Horst-D. 280, 1018
Hummel, R. 1009
Hummel, T. 1049
Hummler, S. 669
Hums, Anna-B. 445
Hüneburg, R. 379
Huober, J. 340, 504, 1027, 1059, 676
Hurvitz, Sara A. 309, 936
Huß, A. 341
Hussain, M. 952
Hussein, M. 16
Hutchinson, J. 307
Hutson, T. 308
I
Ibrahimi, S. 968, 967
Idler, C. 547, 692
Iduna, F. 404
Ihle, P. 934
Ihlow, J. 1026
Ihrig, A. 48
Ihrig, K. 357
Illert, L. 1042
Illes, A. 414
Illmer, T. 476
Im, E. 730
Im, Seock-A. 283
Imkamp, F. 601
Imle, R. 749
Inhestern, L. 871
Inwald, Elisabeth C. 452, 441, 452
Irmer, B. 815
Iro, H. 261, 432, 476
Isfort, P. 119
Isfort, S. 739
Italiano, A. 277
Ito, R. 281, 282
Ivanyi, P. 82, 152, 153, 158,
266, 486
Izbicki, J. 933, 1035
Izquierdo, E. 711
Izutsu, K. 968, 891, 967
J
J. Hall, M. 950
Jackisch, C. 11, 66, 80, 504, 1027
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Oncol Res Treat 2022;45(suppl 1):7–284 Author Index272
Jacob, A. 414
Jacob, Anne S. 339
Jacob, F. 620, 640
Jacob, S. 219
Jacobasch, L. 867
Jaeger, A. 11, 80
Jaehde, U. 635
Jaehn, P. 876
Jaeschke, B. 280
Jafari, A. 921
Jagannath, S. 534, 560, 709, 208
Jäger, B. 785
Jäger, D. 86
Jäger, E. 753, 85
Jäger, M. 586
Jahn, B. 947, 955, 1032, 1016
Jain, R. 446
Jäkel, N. 198
Jakob, Carolin E.M. 1014
Jakob, J. 593, 594, 292
Jakubek, F. 294, 346, 351
Jänicke, M. 67, 135, 211, 246, 259, 280
Janjigian, Yelena Y 1064, 1044
Jann, Johann-C. 12
Janni, W. 11, 80, 340, 656, 658,
954, 1059, 676
Janning, M. 510
Janot-Matuschek, M. 788
Jansen, C. 1037
Jansen, H. 506, 721
Jansen, L. 445, 680
Jansen, L. 358
Janssens, A. 166
Jarczyk, J. 79
Jassem, J. 942
Jechorek, D. 801
Jenner, K. 198
Jensen, Bjoern-E. 1014
Jentschke, E. 386, 419, 485, 1018
Jentschke, M. 102
Jeremias, I. 537, 555
Jerónimo, C. 556
Jerusalem, G. 210
Jeschke, U. 118, 132, 571, 828
Jessen, C. 385
Jewell, A. 1055
Jewell, R. 991
Jhaveri, K. 283, 608
Ji, Jun Ho 908
Ji, M. 374
Jiang, R. 150
Jievaltas, M. 326
Jimenez, B. 990
Jin Hyung, W. 1044
Joachims, J. 156
Jochheim, L. 425
Joedicke, A.s 404
Joedicke, Jara J. 296
Joensuu, H. 952
Johannsen, Lene M. 871
Johannsen, M. 780, 794, 795
John, H. 547
John, J. 751
John, T. 942
John, U. 975, 1022
Johne, A. 370, 840
Johnsen, Steven A. 1
Johnson, Melissa L. 16
Johnston, Patrick B 968, 967
Johnston, S. 436
Joko-Fru, Yvonne W. 716
Jones, B. 829
Jones, David T.W. 829, 628
Joo, S. 1003, 1005
Joos, M. 1065
Joos, S. 692, 720, 951
Jordan, K. 324
Jördens, M. 744
Jost, T. 512, 607
Jou, Ying-M. 971
Joy, S. 547
Jücker, M. 120, 1042
Jucknewitz, R. 621
Juhasz-Böss, I. 341
Jung, A. 537, 555
Jung, L. 659
Jung, P. 1018
Jünger, M. 46
Junghans, K. 198
Junghanß, C. 228, 229, 642
Junker, K. 128, 195, 556
Jurczak, W. 349, 516, 374, 891,
166, 411, 414
Jurgens, H. 450
Jürgensen, C. 855
Just, M. 340, 339
K
K. Homann, T. 131
Kaaks, R. 852, 946
Kaftan, H. 262, 430
Kähler, Katharina C. 267
Kahlmeyer, A. 233
Kähnert, H. 455
Kailayangiri, S. 31
Kaina, B. 43, 52, 53, 768
Kaiser, C. 522
Kaiser, E. 426
Kaiser, S. 612
Kal, Jörg C. 921, 995
Kalinsky, K. 936
Kalka, C. 621
Kallies, A. 476
Kalogirou, C. 79
Kaltenbach, A. 692, 720, 951
Kaltenecker, G. 269
Kalweit, C. 1049, 1052
Kamal, M. 916
Kambartel, K. 1007
Kamdar, M. 968, 967, 166
Kamio, T. 1074
Kämpfe, D. 869
Kamps, M. 591
Kanerva, J. 450
Kantelhardt, Eva J. 716, 751, 823, 198
Kanz, F. 390
Kao, S. 256
Kapitza, P. 983
Kapp-Schwoerer, Silke 956
Kapur, D. 989
Kapusta, N. 996
Karadeniz Cakmak, G. 269
Karapetyan, Armen R. 223
Karlsson, K. 166
Karsten, Maria M. 127, 572
Kaschdailewitsch, E. 547
Kasper, B. 804, 486
Kasper, S. 276
Kasper-Virchow, S. 20, 344, 752, 792
Katalinic, D. 579, 760
Kater, Arnon P. 411
Kates, Ronald E. 870, 899
Kathmann, L. 706
Katzenmeier, M. 912
Kaumann, P. 566
Kaumann-Guerrero, D. 728
Kaufmann, A. 764
Kaul, D. 884, 847
Kaul, H. 339
Kaur, S. 634
Kawaguchi, Y. 1074
Kayali, M. 663
Kazdal, D. 482, 707
Kazmierczak, M. 374
Keam, B. 308
Keck, Maximilian 686
Keck, T. 1009
Keeton, E. 636
Kehrer, H. 73
Keilholz, U. 260, 524, 563, 1026
Keilmann, Lucia K. 132
Kéïta, M. 823
Keller, D. 502, 649
Keller, M. 788
Keller, M. 159
Keller, R. 1007
Keller, U. 681
Kendel, F. 397, 722, 889
Kengelbach-Weigand, A. 607
Keppler, Bernhard K. 1045
Kerek-Bodden, H. 313
Kerkho, A. 345
Kerkmann, M. 945
Kern, J. 16, 280, 1047
Kern, J. 143, 576
Kersten, J. 727
Kersting, S. 46, 761
Keßler, Almuth F. 485
Kessler, M. 118, 132, 571
Kesting, M. 458, 493
Kesting, S. 673, 356
Ketter, L. 426
Keziban, M. 260
Khalmurzaev, O. 556
Khan, S. 309
Khan, W. 281, 282
Khodamoradi, Y. 1041, 1014
khosravian, M. 403
Kiderlen, Til R. 171
Kieback, E. 681
Kiechle, M. 506, 721, 114, 359
Kiermeier, S. 324, 569
Kieschke, J. 354
Kießig, S. 655
Kim, Dong-W. 840
Kim, Hye R. 989
Kim, Sang-W. 16
Kim, Sung-B. 436
Kim, Yu J. 989
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Oncol Res Treat 2022;45(suppl 1):7–284Author Index 273
Kimmig, R. 199
Kim-Wanner, Soo-Z. 300, 398, 675
Kinzel, T. 855
Kirchner, L. 323
Kirchner, T. 537, 555, 749
Kirschner, M. 739
Kiselicki, D. 85
Kislov, N. 33
Kisro, J. 103
Kitz, J. 292, 1077
Klafke, N. 547, 692, 720, 951, 1067
Klamroth, R. 621
Klapdor, R. 601, 629, 1015
Klar, M. 341
Klauschen, F. 537, 555
Klautke, G. 63
Klautke, G. 476
Kleihues-van Tol, K. 515, 531
Kleihus van Tol, K. 1009
Klein, A. 313, 705, 762
Klein, A. 773
Klein, E. 114
Klein, Florian G. 929, 1024
Klein, K. 722
Klein, M. 739
Klein, M. 934
Kleinman, D. 991
Klier, J. 780, 794, 795
Klinghammer, K. 243
Klinkhammer, H. 379
Klinkhammer-Schalke, M. 903, 515, 531,
462, 355, 1009,
441, 492, 452, 1039
Kloess, A. 515
Klopp, N. 416
Kloppe, T. 934
Klotz, Laura V. 413, 707
Klotz, R. 165, 1065
Kluba, T. 410
Kludt, E. 415
Klug, S. 764
Klümper, N. 79, 551
Klußmann, Jens P. 446
Klüter, S. 578
Knapp, I. 724
Knauf, Wolfgang U. 252, 523, 1039
Knebel, P. 1065
Kneis, B. 761
Knobloch, J. 627
Knoefel, Wolfram T 744
Knoop, H. 610
Knop, S. 534
Knopf, A. 454, 646
Knösel, T. 219
Knott, Maximilian M. L. 749
Ko, Yon-Dschun 635
Kobe, C. 339
Kobelt, D. 605
Koch, A. 568
Koch, A. 102
Koch, B. 731
Koch, B. 900
Koch, L. 544
Koch, M. 758
Koch-Gallenkamp, L. 532
Koch-Gromus, U. 616
Köditz, B. 661, 701, 711
Koeberle, D. 103
Koeditz, B. 698, 708, 715
Koepke, Leon-G. 895
Koerber, Stefan A. 36, 852
Koerdel, K. 1
Kohler, R. 381
Kohler, S. 692
Köhler, H. 689
Köhrer, K. 149
Kokh, D. 392
Köksal, M. 921
Kolbe, Ernst W. 170
Kolbe, L. 594
Kolben, T. 132, 571
Kolben, T.s 118, 132, 571
Kolberg, Hans-C. 608, 157
Kolberg-Liedtke, Co. 157
Kölbl, O. 111, 146
Kolk, A. 1024, 929
Kollikowski, A. 735
Kollmar, O. 89, 104
Kollmeier, J. 416, 518, 1047
Kölsch, H. 1032
Kömpel, T. 974, 987
Komrokji, Rami S. 281, 282
Konczalla, L. 933, 1035
Konecny, Gottfried. E. 636
Koneval, L. 233
König, A. 298
König, F. 780, 794, 795
König, Julia Felicitas L. 467
König, L. 47, 234, 244, 360,
500, 578, 851
König, T. 823
Könsgen, N. 914
Kontos, M. 269
Kopp, Hans-G. 486, 410
Köppel, M. 614, 617, 630, 741
Kopyltsov, E. 308, 328, 952
Korach, J. 654
Korshunov, A. 737
Korus, B. 1067
Kosanke, G. 767
Koska, M. 67
Kost, B. 828
Kostbade, K. 276, 344, 752
Koster, J. 201
Kotarac, A. 260, 563
Kotzerke, M. 156
Kouam-Daniel, P. 783
Kouka, M. 430
Kourti, E. 449, 816, 523
Kovac, M. 628
Kovács, L. 180
Kowalski, C. 127
Koziorowski, A. 606, 433
Kozlov, V. 308
Krabbe, Laura-M. 253
Kraeft, Anna-L. 788, 1039, 816, 523
Kraemer, A. 36
Kragl, B. 228
Kramberg, S. 1066
Kramer, M. 134, 702
Krämer, A. 223
Krämer, A. 191, 500
Krämer, A. 380
Krammer-Steiner, B. 103
Krassnig, S. 404
Kratzer, V. 621
Kratzsch, T. 404
Kraus, F. 433
Krause, C. 204
Krause, F. 1
Krause, J. 933
Krause, K. 975
Krause, Luisa C. 134
Kraus-Tiefenbacher, U. 522
Krautz, C. 761
Krawczyk, N. 785
Krawitz, P. 379
Kray, S. 727
Krebs, S. 90
Kreidt, D. 416, 622
Kreissl, S. 610
Krekeler, C. 345, 815
Kreklau, A. 190
Krell, V. 159, 617, 741, 791
Kremeike, K. 634
Kretz, T. 152
Kreuter, A. 267
Kreutz, C. 1040
Kreutz, R. 159
Kreutzer, E. 957
Kreutzer, J. 1071, 1069, 1006, 1075,
1077, 866, 1073
Kreuzwieser, F. 724
Kricheldorf, K. 739
Kriegs, M. 120
Kriegsmann, K. 957
Kriegsmann, M. 413, 707
Krijgsveld, J. 749
Kristeleit, R. 730
Kristiansen, G. 79, 852
Kriston, L. 312
Krivak, T. 636
Kröger, Anne-C. 718
Kröger, B. 547, 692, 720, 951
Kroiher, D. 735
Kroiss, M. 277
Krokenberger, M. 272
Krolo, F. 975, 1022
Krombholz, A. 765
Kronsteiner, D. 191, 500
Krueger, U. 260
Krug, K. 204
Krug, S. 403, 425
Kruggel, L. 245, 246
Krumme, J. 180
Kryachok, I. 414
Kuba, K. 5
Kubuschok, B. 669, 63, 239
Kuczyk, M. 852
Kudak, A. 36, 191, 234
Kueenburg, E. 534
Kufeld, M. 847, 884
Kuhl, C. 119
Kühl, R. 630
Kuhn, Susanne Antje 404
Kühn, F. 127, 572
Kühn, R. 325
Kühn, T. 656, 658, 269
Kühne, F. 1032
Kühne, T. 450
Kuhn-Friedrich, N. 99
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Oncol Res Treat 2022;45(suppl 1):7–284 Author Index274
Kulik, A. 405
Kumar, A. 674
Kumar, Y. 933
Kumas, L. 721
Kumbrink, J. 555
Kümmel, S. 870, 877
Kunadt, D. 874
Kuner, T. 1008
Kunitz, A. 486, 410
Kunz, B. 23
Kuon, J. 413, 482, 707
Kupczyk, M. 613
Kupper, A. 492
Küpper-Nybelen, J. 934
Kuptsova-Clarkson, N. 411
Kurreck, A. 624
Kürschner, D. 410
Kurunci-Csacsko, E. 580
Kusch, M. 313, 705, 717,
743, 762, 844
Kuske, A. 306
Kuss, I. 326, 952
Kusterer, L. 1035
Kütting, F. 425
Kutz, Chiara-S. 607
Kuziora, M. 218
Kyjacova, L. 388
L
L. Kindler, H. 950
La Torre, I. 287
Laack, E. 265
Laban, S. 739, 131, 476
Labouvie, H. 313, 705, 717,
743, 762, 844
Lacko, A. 436
Lai, Z. 218
Lai, Z. 911
Laitman, Y. 361
Lakes, J. 852
Laktionov, K. 16
Lamanna, N. 349, 374, 516
Lambrecht, M. 946
Lammert, A. 143, 576
Landgraf, L. 31
Lang, K. 234, 360, 557
Lang, M. 426
Lange, S. 639
Lange, T. 120
Langer, A. 669
Langer, C. 63
Langer, T. 914
Langer, T. 934
Langhammer, S. 117, 209
Langhans, V. 506
Langheinrich, Melanie C. 761
Lanowska, m. 294, 346, 351
Lantzsch, T. 751
Lanznaster, J. 873, 1014
Lapshyn, H. 1009
Larmann, J. 1065
Larsen, Jeremy T. 534
Lashgari, M. 783
Laskin, J. 277
Lau, A. 499
Laue, K. 276, 344, 752
Laumen, H. 403
Lawler, S. 758
Lawrenz, W. 625
Layer, M. 547, 692
Lazica, D. 42
Le Berre, Marie-A. 326, 327
le Coutre, P. 229
Le Gouill, S. 516
Le Nouveau, P. 691
Le Tourneau, C. 906, 916
Leath III, C. 730
LeBlanc, R. 971
Lebret, T. 327
Lech-Maranda, E. 349
Lechpammer, S. 654
Lederer, J. 758
Ledger, D. 989
Lee, Jae H. 414
Lee, J. 1064
Lee, Jong-S. 920
Lee, Keun-W. 1064
Leerho, S. 170
Leha, A. 1075, 1006, 1069, 866,
1071, 1073, 1, 1077
Lehmann, J. 428, 502, 649
Lehnhardt, M. 251
Lehrach, K. 1066
Lehrke, R. 847
Leibbrand, B. 455
Leibner, M. 204
Leinert, E. 656, 658
Leisegang, M. 681
Leitch, S. 956
Leitsmann, M. 204
Leleu, X. 691
Leleu, X. 971
Lemmen, C. 717
Lendowski, S. 449
Lennartz, M. 1053
Lenton, D. 956
Lenz, G. 345
Lepping, L. 149
Leppla, L. 180
Leprivier, G. 749
Lerchenmüller, C. 259
Letsch, A. 169, 172, 660, 725, 976
Leu, M. 78, 101, 227, 713, 747,
757, 776, 584
Leukers, P. 788
Leuteritz, K. 699
Levchenko, E. 33
Levy, T. 674
Lewis, D. 349, 516
Lewis, K. 516
Lewitzki, V. 262
Li, J. 749
Li, L. 920
Li, R. 952
Li, W. 1003, 1005
Li, Y. 674
Liam, Chong Kim 840
Liang, Ching-Y. 620
Liberati, Anna M. 150
Lichtensteiger, C. 551
Licour, M. 256
Lieb, S. 425
Liebel, K. 143
Liebs, S. 260, 563, 1026
Liersch, R. 33
Liersch, T. 866, 1006, 1069, 1071,
1073, 1075, 1077
Lies, M. 646
Liers, Sven-T. 752, 792
Lihou, Christine F. 335
Lim, Farah L. 16
Limberger, B. 399, 643
Lin, Aimee K. 255
Lin, Nancy U. 210, 309
Lin, Y. 560, 709
Linde, H. 259
Lindenmaier, P. 11, 80
Linderkamp, F. 167
Lindert, T. 788
Lindig, A. 312, 418
Lindley, A. 335
Lindner, L. 219, 486
Lindörfer, D. 947, 955, 1016
Lindsay, J. 150
Ling, T. 991
Lingohr, P. 921
Lingua, A. 942
Link, H. 1036
Link, T. 504, 1027, 1050
Linnebacher, M. 535, 718
Lipfert, Lisa-M. 662
Lippach, K. 49
Lippert, H. 742, 759
Liu, B. 10
Liu, Fei Fei 968
Liu, W. 690, 700, 989
Liu, X. 486
Liu, Y. 956
Livingstone, E. 267
Lobo, J. 556
Loeer, C. 735
Loertzer, H. 556
Loges, S. 369, 510
Löhberg, C. 676
Löhden, I. 238
Lohmann, A. 614
Lohmüller, L. 720, 951
Lohneis, P. 428
Lohse, S. 556
Loi, S. 283, 608, 1027
Loibl, S. 309, 504, 1027, 114, 936
Loirat, D. 936
Lonial, S. 534, 709, 208
Loong, H. 255
Loosen, S. 744
Lopez, Pilar G. 989
Loquai, C. 73
Lorch, A. 152, 158
Lordick, F. 699, 787, 1023,
1064, 1062
Lorenz, A. 66
Lorenz, A. 548
Lorenzen, S. 357
Lorocca, A. 150
Lorusso, D. 1050
Losa, F. 223
Losem, C. 574
Löser, H. 428
Löser, H. 810
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Oncol Res Treat 2022;45(suppl 1):7–284Author Index 275
Loskutov, J. 325, 366, 684, 718
Lösse, V. 575, 987
Lowinus, T. 307
Lu, S. 942, 840
Lübke, Andreas M. 1053
Ludescher, M. 748
Ludwig, A. 399, 643
Ludwig, C. 198
Ludwig, S. 576, 143
Luedde, T. 744
Luerken, L. 813
Luft, A. 16
Lüftner, D. 66
Lugnier, C. 523, 788, 1039, 816
Lüke, C. 156
Lunning, M. 968, 967
Lupinacci, L. 920
Lüpkes, C. 934
Lurati, Magalie C. J. 1029, 1031
Lusky, F. 482
Lutz, R. 458, 493
Lutze, S. 46
Luz, M. 326
Lynch, C. 309
Lyros, O. 697, 399, 643
Lysak, D. 414
M
M. Kraus, J. 131
M. O‘Reilly, E. 950
Maag, Teresa E. 747, 757
Maas, L. 625
Maas, L. 502
Maas, V. 136, 659, 575
Maasberg, M. 82
Maass, Kendra K. 829
Maass, N. 169, 172
Maatoug, Y. 701
Maatouk, I. 324, 360, 569
Macarulla, T. 950
Mach, P. 199
Machmer, T. 191
Mackensen, A. 31
Maenz, M 1047
Maghnouj, A. 897
Mahler, C. 692, 720, 951
Mahn, R. 921, 995
Mahner, S. 118, 571, 114, 359,
298, 828, 132
Mai, K. 159
Maier, A. 1030
Maier, S. 297
Maintz, C. 82, 245
Mairinger, E. 199, 416, 518, 622
Mairinger, Fabian D. 199, 416, 518, 622
Mairinger, T. 518, 416
Maj, C. 379
Majchrzak-Stiller, B. 814
Makowski, M. 852
Maktabi, M. 689
Malinka, T. 624
Malinowska, I. 674
Mallm, Jan-P. 737
Maloney, D. 967
Mamlouk, S. 325
Man, S. 562, 727
Mańczak, A. 921
Mandelkow, T. 1054, 1053, 1031, 1029
Mandrella, M. 594
mangler, m. 294, 346, 351
Manier, S. 560
Mann, H. 908
Mann, J. 731
Mann, M. 929
Mannewitz, M. 132, 571, 118
Mannsmann, V. 171
Mansmann, U. 621, 947, 955, 1016
Mansy, T. 868
Mantovani, E. 281, 282
Mantsopoulos, K. 261
Mantwill, K. 929, 1024
Manz, K. 862
Mänz, M. 152, 1007
Marass, F. 745
March, C. 604
Marchetto, A. 749
Marheinecke, Corinna S. 449
Maria, W. 21
Mariani, M. 151
Marinova, M. 995
Märkl, B. 669
Markus, M. 594
Markus, P. 276, 344, 752
Marmé, F. 504
Maroto, P. 308, 158
Marquardt, Jens U. 443
Marschall, U. 934
Marschner, N. 67, 246, 259
Martel, J. 268
Marten-Mittag, B. 359
Martens, U. 67, 166, 906, 916
Marti Grifol, C. 697
Martin, M. 436
Martinez-Marti, A. 33
März, M.l 146
Maschmeyer, G. 262
Masini, C. 222
Maßmann, M. 344, 752
Matasar, M. 891
Mathies, V. 961, 1056
Mathilakathu, A. 416, 622
Mathys, B. 354
Mato, Anthony R. 516, 411, 349
Matsuda, T. 117
Matthes, B. 964
Matthes, H. 299
Matthews, C. 730, 1050, 1055
Matulonis, U. 654
Matveev, V. 556
Maulbecker-Armstrong, C. 940, 941
Maurer, G. 567
Maurer, J. 931
Maurer, L. 159
Mauz, Paul-S. 63
Mavroeidi, Ilektra-A. 792
Mawrin, C. 474
May, P. 379
May, S. 167
Mayer, A. 1057
Mayer, B. 586
Mayer, F. 410
Mayer, J. 374
Mayr, A. 379
Mayr, D. 828, 114
Mazieres, J. 868
Mboni Johnston, Isaac M. 490
McAdoo, W. 1064
McCormick, C. 674
McDonald, F. 256
McKeown, A. 991
McKiver, Mihaela P. 971
McNally, V. 33
Medic, N. 16
Mehlis, K. 961, 415
Mehnert, A. 1062
Mehnert-Theuerkauf, A. 5, 610, 616,
857, 1030
Mehta-Shah, N. 891
Meier, F. 73, 456
Meier, I. 934
Meier-Stiegen, F. 676
Meiler, J. 152, 153
Meinhardt, G. 1074
Meisel, Hans-J. 474
Meiss, F. 307
Meissner, Valentin H. 92
Meister, M. 482
Meister, S. 118, 132, 571
Meixner, E. 234, 851
Melcher, I. 410
Melichar, B. 308
Mellado, B. 158
Melling, N. 933, 1035
Menck, K. 345, 808, 815
Mende, B. 344, 752
Mende, S. 36
Mendes Wefelnberg, M. 772
Mendrina, T. 1045
Meneceur, S. 149
Menevse, Ayse N. 613
Menezes, D. 287
Menezes, J. 942
Menold, N. 1056, 961
Menrath, I. 673
Mentrup, S. 660, 725
Mercade, Teresa M. 714
Merkel, S. 864
Merkelbach-Bruse, S. 912
Merker, S. 510
Merle, P. 32
Mertens, I. 547
Mertins, P. 260, 524, 605
Merzenich, H. 997
Mess, Elisabeth V. 180
Messina, C. 902
Metz, M. 152
Metzeler, K. 537
Metzergoth, G. 12
Meye, H. 522
Meyer, C. 94, 1022, 975, 562
Meyer, F. 604, 609, 736, 738,
742, 759, 781,
793, 801, 809
Meyer, J. 829
Meyer, M. 86
Meyer, M. 618
Meyer, N. 914
Meyer, O. 869
Meyer, T. 1
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Oncol Res Treat 2022;45(suppl 1):7–284 Author Index276
Meyer-Knees, J. 624
Meyer-Schwickerath, C. 321
Mezger, N. 716, 823
Michels, B. 1006, 1071
Michels, S. 912
Michielin, O. 73
Michl, P. 403
Micke, O. 410
Mielke, S. 690, 700, 967
Migliorino, Maria R. 868
Migotti, R. 605
Mihaljevic, A. 165
Mikesch, Jan-H. 268
Mileshkin, L. 223
Miller-Phillips, L. 537
Mink, J. 556
Minner, S. 1031, 1053
Minto, Carrie-A. 731, 735, 826
Miranda, P. 411
Mirza, M. 654
Misiak, D. 403
Miskic, M. 327
Miteva, D. 281, 282
Mitter, S. 132, 571
Mix, M. 591, 513
Mizutani, H. 942
Mocek, A. 862
Moch, H. 223
Modi, A. 1001
Modrok, M. 568
Mogwitz, R. 639
Mohammad, Nadia H. 1064
Mohr, P. 267
Mohr, R. 425
Mohr, T. 1045
Möhring, C. 921, 995
Mok, T. 16
Mokritzkij, M. 524
Moldenhauer, G. 86
Molena, D. 1044
Möller, K. 1054
Momburg, F. 86
Monin, M. 921
Monk, Bradley J 654, 674
Mönnigho, U. 519
Montesa Pino, A. 952
Montesinos, P. 287
Montheard, S. 968, 967
Moore, K. 654
Moore, Richard. G. 674, 636
Morakis, P. 177, 390, 392
Moran, D. 117
Moratin, J. 360
Morawietz, C. 321
Moreau, P. 150, 709, 971, 208
Morgan, M. 629
Moritz, Rose C.K. 198
Moritz-Tugral, R. 801
Mornex, F. 256
Morris, P. 504
Morschhauser, F. 891, 967
Mörtl, B. 779
Moser, K. 940, 941
Motzer, R. 308
Moy, B. 553
Muacevic, A. 847, 884
Muders, M. 79
Muegge, Lars-O. 229
Muehlan, H. 655
Muehlensiepen, F. 167
Mueller, Daniel W. 85
Mueller, L. 132
Muenst, S. 89
Mühlberger, N. 947, 955, 1032, 1016
Muley, T. 413, 482, 707
Müller, A. 430
Müller, A. 128
Müller, C. 426
Müller, C. 59, 425
Müller, G. 381
Müller, H. 398
Müller, H. 610
Müller, Jan H. 1029, 1031
Müller, J. 1040
Müller, L. 571
Müller, L. 561
Müller, L. 676, 152, 67
Müller, S. 261, 432
Müller, T. 635
Müller, T. 814
Müller, V. 267
Müller, V. 11, 66, 80, 210, 283,
340, 954, 676
Müller-Huesmann, H. 103, 265, 266, 63
Müller-Nordhorn, J. 618
Müller-Schuchardt, A. 456
Mullins, C. 535
Mumm, F. 297, 359
Munhoz, E. 891
Munir, T. 166
Munoz, M. 436
Munshi, Nikhil C. 709, 208
Münstermann, J. 686
Münter, M. 262
Munugalavadla, V. 166
Muraro, Manuele G. 104
Murawa, D. 269
Muro, K. 1044
Murthy, Rashmi K. 309
Murua Escobar, H. 642
Musa, J. 749
Mustafa, B. 897
Muster, J. 78, 227
Musuraca, G. 414
Müther, M. 943
Mutsaers, P. 968, 967
Mykhalska, L. 891
N
Naendrup, Jan-H. 767
Nagels, K. 391
Nano, D. 90
Napp, J. 293
Narasimhan, H. 931
Nath, A. 416
Nathrath, M. 628
Nauck, F. 757
Naumann, C. 198
Naumann, P. 47, 244
Nawroth, R. 1024, 929
Nees, J. 569
Negrier, S. 158
Negro, A. 1044
Nekljudova, V. 1027, 114
Nel, I. 190
Nennecke, A. 238, 532
Nestler, T. 701, 711
Neubauer, A.s 726
Neubauer, H. 380, 405, 590,
740, 745, 748
Neuberger, P. 547
Neubert, S. 386
Neuhaus, B. 102
Neumann, C. 624, 1026
Neumann, Ulf P. 627
Neumann-Stern, C. 134
Neuser, P. 300, 398
Neustadt, A. 198
Neuwirth, E. 873
Ng, F. 621
Nguemeni, C. 385
Nguyen, Tuong V. 534
Nguyen, Van A. 544
Nicholas, A. 32
Nickel, E. 111
Nicol, D. 701
Nicolay, Nils H. 140, 191, 454, 460, 513, 646
Niederacher, D. 380, 405, 561, 590,
740, 745, 748, 785
Niegisch, G. 82, 149
Niehues, T. 625
Niels, T. 20, 617, 741, 767, 773
Niethard, M. 366, 678
Nietzio, A. 724
Niikura, N. 283, 210
Niinikoski, L. 269
Nikendei, C. 360
Nilius, G. 606, 433
Nishio, M. 920
Nitsch, T. 873
Noack, B. 494
Noething, C. 586
Nogova, L. 912
Nolting, J. 23, 21
Nöpel-Dünnebacke, S. 523, 788
Nordt, C. 46
Nothacker, M. 914
Nöthen, M. 379
Noujaim, J. 690, 700
Novello, S. 989
Novotny, W. 374
Nowak, A. 198
Nowak, D. 12
Nowicki, M. 758
Nowotny, R. 697
Nuhn, P. 79
Nunez-Lopez, M. 620
Nusch, A. 67, 246, 867
Nyanchama, M. 716
O
O’Byrne, Kenneth J. 920
O’Shaughnessy, J. 936
Oakman, C. 309
Oaknin, A. 730, 990, 1055
Oberhoer-Fritz, R. 356
Oberic, L. 891
O‘Brien, S. 374, 411
O‘Cearbhaill, R. 674
Ochsenreither, S. 370, 681
Downloaded from http://karger.com/ort/article-pdf/45/Suppl. 3/6/4143722/000521004.pdf by guest on 05 March 2024
Oncol Res Treat 2022;45(suppl 1):7–284Author Index 277
Ockert-Schön, F. 655
Odenthal, M. 817
Oechsle, K. 634, 976, 1062
Oehme, I. 749
Oei, Shiao L. 299, 964
Oertel, M. 268, 573
Ogasawara, K. 967
Ogrodnik, Simon J. 482
Oh, Do-Y. 950, 1064
Oh Park, J. 950
Oh-Hohenhorst, Su J. 972
Ohlmann, C. 881, 945
Ohlrogge, C. 472
Okera, M. 436
Okonechnikov, K. 737
Oksentyuk Polyakova, T. 604, 781
Oksuzoglu, B. 436
Oliveira, M. 936, 309
Olmos, M. 493
O‘Malley, D. 674, 730, 1055
On, J. 405
Ooms, M. 739
Opalinska, J. 991
Oriol, A. 150, 534, 709
Orth, Martin F. 749
Orthmann, A. 404
Ortiz, J. 328
Ortmann, O. 452, 611, 441, 903, 347
Ortner, P. 288, 298
Oschwald, V. 136, 575, 659, 974, 987
Oscroft, E. 210
Osterland, M. 388
Ostermann, H. 369, 621
Osumi, H. 260, 563
Oswald, H. 744
Oswald, J. 462
Otremba, Burkhard J. 239
Otten, S. 136, 974, 987
Ottensmeier, C. 131
Otto, G. 370
Otto, R. 809, 759
Ou, X. 950
Oubaid, N. 634
Ouedraogo, N. 940, 941
Oughton, J. 902
Ouyang, Q. 436
Overbeck, T. 370
Overheu, O. 449
Overkamp, F. 385, 553
Oya, M. 151, 308
Oyelami, F. 329
Ozga, Ann-K. 731
Özgüroğlu, M. 908
P
Pabst, T. 339
Pachmayr, E. 524
Pacíco, C. 1037
Paenholz, P. 701
Pagel, John M. 349, 516
Paik, Paul K. 370
Pajtler, Kristian W. 829, 737
Pallasch, C. 711
Palomba, M. Lia 516
Pamuk, A. 810
Panic, A. 158
Panse, J. 218
Panse, J. 1041
Panse, J. 116, 911
Pantel, K. 954, 1035, 676
Papadopoulos, N. 294, 346, 351
Papazisis, K. 436
Pardo, L. 566
Park, Chandler H. 952
Park, K. 255
Parks, D. 1050
Park-Simon, Tjoung-W. 436
Parnis, F. 952
Pascher, A. 345
Passlick, B. 135
Passmann, E. 912
Patel, Manish R. 349, 516
Patel, N. 690, 700
Patel, P. 709
Patel, R. 690, 700
Patre, M. 283
Pauer, A. 355, 441, 492, 903, 452
Pauge, S. 961, 1056
Pauker, W. 42, 109, 186, 479
PAUL, A. 276, 344, 752, 792
Pauli, C. 223
Pauligk, C. 357
Pausch, Thomas M. 1002
Pawandenat, C. 874
Pawlak, M. 590
Pawlowska-Phelan, D. 862
Paz-Ares, L. 116, 868, 908,
920, 942, 911
Pazgan-Simon, M. 714
Pedersoli, F. 119
Peeck, M. 345, 815
Peifer, M. 502
Peintinger, F. 269
Péko, Jean-F. 716
Peluso, T. 150
Pelzer, U. 624, 1026, 1049, 1052
Penkov, K. 989
Pereira, P. 211
Perez, D. 933
Perez, Ignacio D. 868
Perez, L. 916
Pérez-Fidalgo, Jose-A. 674
Perez-Hernandez, D. 605
Perkhofer, L. 1003
Perl, T. 529
Perleberg, C. 118
Perner, F. 323
Perrakis, A. 809
Perret, C. 906, 916
Perrot, V. 222
Peschel, S. 751
Peters, C. 356
Peters, I. 814
Peters, I. 852
Peters, S. 46
Peters, S. 16, 337, 218, 256
Petersen, M. 781
Petersen, V. 280
Petricoin III, E. F 1005, 1003
Petrova, E. 1009
Petzsch, P. 149
Pezzutto, A. 681
Pfänder, S. 449
Pfeilstöcker, M. 287
Pster, K. 1059
Pster, Stefan M. 829, 749, 201, 737
Paume, A. 524, 684
Pfohl, U. 325, 718
Pföhler, C. 267, 648
Pförtner, Timo-K. 44
Phan, See-C. 936
Philipp, Lisa-M. 179, 490, 1001
Philipp, R. 871
Piccart-Gebhart, M. 936
Pichler, T. 297, 359
Piee-Staa, A. 52
Pieper, D. 914
Pietzner, K. 291, 302
Pigorsch, S. 359
Pilarsky, C. 678
Pink, D. 702, 804
Pinter, M. 425, 443
Pinto, A. 891
Pinto, D. 269
Pirker, C. 1045
Pirmorady, A. 159
Piscuoglio, S. 89, 104
Pishvaian, Michael J 1003, 1005
Piskorski, L. 578
Piso, P. 355, 1039
Placke, Jan-M. 307
Plathe-Ignatz, C. 634
Platzbecker, U. 5, 281, 282, 610, 956
Ploner, T. 862
Pluetschow, A. 339
Plum, Patrick S. 1002
Pluta, A. 414
Poehler, M. 751
Pogorzelski, M. 276, 344, 752
Poltoratskiy, A. 908
Polyakov, S. 326
Polzer, B. 380
Poole, L. 16, 218
Popat, R. 534
Popp, F. 428
Popp, I. 454
Popp, O. 524, 605
Popper, U. 103
Porat, Y. 460
Porst, J. 159, 791
Porta, C. 308
Poschke, I. 482
Possiel, J. 101, 713, 776
Pothuri, B. 730, 1055
Pott, C. 638, 679
Pottho, K. 211, 245
Powers, B. 690, 700
Powerski, Maciej J. 59
Powles, T. 308
Prager, G. 867, 103, 335
Pramatarov, R. 1008
Prate, K. 874
Pratschke, J. 624, 1026
Preissler, Bastian I. 198
Prenzel, R. 694
Press, J. 730
Pretzsch, E. 219
Preugszat, E. 428, 649
Previtali, A. 968, 967
Priesch-Grzeszkowiak, B. 783
Priese, J. 445
Priselac, K. 1037
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Oncol Res Treat 2022;45(suppl 1):7–284 Author Index278
Pritzkuleit, R. 532
Procopio, G. 222, 308
Proescholdt, M. 815
Prokakis, E. 588
Prokop, A. 136, 673
Pross, T. 127, 572
Protsenko, S. 942
Prugger, V. 351, 346
Pryalukhin, A. 556
Przybylla, R. 535
Ptok, H. 738, 809, 736
Ptok, J. 561
Pukrop, T. 815
Pullankavunkal, J. 346, 351, 294
Püllen, L. 507
Punie, K. 936
Puranachot, P. 829
Puri, T. 255
Püschel, L. 660
Q
Qian, Y. 10
Qiu, L. 374
Quaas, A. 428, 446, 502, 649, 810, 812
Quaester, S. 179, 490
Quast, Daniel R. 449
Quiering, C. 1004
Quinn, D. 151
R
Raab, Marc-S. 971
Raab, M. 565, 580
Rabe, A. 386, 419, 485, 1018
Rachow, T. 100
Raciborska, A. 450
Rack, B. 340, 954, 1059, 676
Rademacher, A. 737
Radtke, Jan P. 852
Radulovic, I. 561
Radziwill, R. 754
Raem, Arnold M. 170
Rafei-Shamsabadi, D. 307
Rayan, Mohammad-R. 85, 152
Rafyian, R. 82
Rahat, Michal A. 329
Rahn, Anne C. 660, 725
Rahn, S. 179
Rai, S. 891
Raja, R. 218
Rajagopal, R. 956
Raje, N. 560, 709, 208
Ramaker, K. 269
Ramalingam, S. S. 337, 920
Ramanathan, S. 956
Rambaldi, A. 709
Ramos, J. 309
Ramroth, H. 252
Rancati, T. 946, 970
Ranft, A. 450
Ranogajec, I. 579
Rapp, M. 398
Räpple, S. 903
Rascon, J. 450
Rasenberger, B. 768
Rath, Hilke M. 976
Rattay, T. 946
Rau, B. 388, 524
Rau, Bettina M. 492
Rauch, J. 359
Raue, Jan S. 1030
Rawluk, J. 218
Reck, M. 135, 868, 920, 942, 1007, 1047
Reder, H. 446
Reece, D. 709, 208
Reeh, M. 1035
Reetz, K. 1023
Reeves, J. 436
Regenbrecht, C. 325, 366, 524,
678, 684, 718
Regenbrecht, M. 366
Regnery, S. 47, 191, 244, 360, 578
Rehm, A. 296
Rehms, R. 947, 955, 1016
Reich, F. 94
Reich, V. 855
Reichelt, R. 306
Reichenbach, F. 103, 260, 867
Reichert, D. 67
Reinacher-Schick, A. 449, 523, 788, 799,
816, 950, 1039
Reinert, S. 352
Reinhard, C. 325, 366, 684
Reinhardt, D. 2, 625, 1060
Reinhardt, F. 745
Reinhold, T. 159
Reinisch, M. 504, 309, 1027
Reinmuth, N. 16, 370, 868, 908,
942, 1007
Reinwald, M. 171
Reis, H. 507, 518
Reis, Joschua M. 419
Reiser, M. 135, 259, 869
Reißig, T. 792
Reitz, M. 974, 987
Relógio, A. 302
Rémy, R. 44
Ren, H. 219
Rengsberger, M. 100
Reni, M. 950
Renkamp, C. Katharina 578
Retz, M. 945
Reulen, Hans-J. 943
Reuter, B. 63
Reuter, H. 857
Rexer, H. 29
Rey, J. 504
Reyes, F. 942
Rezai, M. 429
Rhein, S. 243, 681
Rhiem, K. 44, 1027
Ribaut, J. 180
Richards, Elisabeth C. 335
Richardson, D. 636
Richardson, P. 150, 534, 971
Richter, D. 699
Richter, L. 961, 1056
Richter, P. 986
Richter, R. 716
Richter, S. 804, 486
Richter, T. 655
Richtig, E. 73
Ridwelski, K. 759, 793
Ried, K. 611
Riedel, R. 912
Rieder, N. 976
Rieken, S. 34, 47, 78, 101, 227,
244, 360, 500, 713, 747,
757, 776, 583, 584
Riemenschneider, Markus J. 613
Riera Knorrenschild, J. 726, 63
Ries, J. 458, 493
Rieser, T. 299
Riess, H. 624
Riethdorf, S. 676, 1035
Rimmer, N. 620
Rinnerthaler, G. 66
Rippe, K. 737
Rippke, C. 578
Ristau, J. 578, 36
Risueño, A. 287
Ritschel, Maria-L. 682
Ritter, C. 655
Ritter, M. 79, 551
Ritter, T. 1006, 1069, 1071, 1073, 1077
Rittmeyer, A. 1007
Rivandi, M. 380, 590, 740, 745
Rizvi, N. 218
Robak, P. 150
Robbins, Scott H. 1044
Robinson, B. 277
Robold, T. 462
Roboz, G. 287
Robrahn, L. 627
Roca Ripoll, B. 611
Röcken, C. 209
Roderburg, C. 744
Rodriguez-Lopez, K. 308
Rodriguez-Otero, P. 534, 560
Roeker, Lindsey E. 349
Roeper, J. 694, 706, 712
Rogahn, J. 228
Rogge, T. 808
Roggendorf, S. 499
Roghmann, F. 79
Rohrer, P. 544
Röhrle, J. 344, 752
Rohrmus, C. 613
Roll, S. 159
Roll, W. 943
Rolland, F. 308
Rolles, B. 739
Rolo, D. 99
Romero-Perez, L. 749
Ronellentsch, U. 593
Roob, D. 851
Roos, F. 128
Rose, M. 159, 291
Rosé, C. 260
Rose-John, Stefan. 1
Rosenstein, B. 970, 946
Rosenwald, A. 339
Rosery, Vivian K. 344, 276, 752
Ross, G. 283
Ross, Jerey S. 223
Rossdam, C. 620
Rössig, C. 31
Rößler, M. 515, 531
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Oncol Res Treat 2022;45(suppl 1):7–284Author Index 279
Roth, J. 627
Rotmann, A. 769
Rotter, N. 576, 143, 262
Rottey, S. 158
Rowe, E. 560, 208
Rubio, Isabel T. 269
Rübner, M. 31
Ruckes, C. 1057
Ruckhäberle, E. 785, 676
Ruckriegl, S. 588
Rudert, M. 410
Rudin, Charles M. 911
Rudolph, I. 615
Rueegg, Corina S. 625
Ruescho, J. 810
Rueß, D. 847
Ruf, F. 269
Ruf, J. 513, 591
Ruge, M. 847
Rugo, H. 936
Rühl, R. 568
Rühle, A. 140, 454, 460, 513, 646
Rühlmann, K. 537, 555
Ruhnke, T. 531
Rummel, M. 252
Rummeny, E. 852
Runnebaum, Ingo B. 662, 680
Rupp, R. 261
Ruscica, D. 1044
Rüthrich, Maria M. 1014, 1041
Rutty, D. 1036
Ryabov, V. 12
S
Saad, F. 952
Saalfeld, F.C. 510
Saal, J. 79, 551
Sabatier, R. 730, 1055
Sadeghlar, F. 921, 995
Sadewasser, K. 1022
Sadjadian, P. 1007, 1047
Safaei, R. 523, 788
Sagasser, J. 340
Sahi, D. 980
Sahlmann, Carsten-O. 1077, 1069
Sahm, F. 829
Saito, H. 16
Saito, K. 308
Saito, T. 117
Sakai, H. 370
Salameh, R. 593
Salat, C. 306
Salchow, J. 731, 735, 826
Salem, R. 32
Salgueiro, L 510
Salim, Hizirwan S. 119
Sallach, N. 169, 172
Salles, G. 891
Salm, H. 702
Salmi, T. 374
Salomon, Arne G. 171
Salwender, H. 991
Samatin, Fana-L. 198
Samouelian, V. 730, 990, 1055
Sánchez, José Garcia 868
Sanchin, L. 474
Sandrini, E. 851
Sanford, J. 560
Sangha, R. 920
Sanhaji, M. 565, 580
Sankarasubramanian, S. 678, 718
San-Miguel, J. 150, 208, 709, 971
Santini, V. 281, 282
Sarapohja, T. 326, 328
Sarria, Gustavo R. 921
Sastre, A. 749
Saternus, R. 648
Sätzler, R. 1066
Sauer, C. 360
Sauer, G. 1041
Sauer, R. 366
Sauer, S. 957
Sauerland, S. 1032
Sauter, G. 1053, 1031, 1029
Sautier, L. 616
Sawyer, W. 256
Schaaf, M. 85
Schaal, H. 561
Schad, F. 299, 497, 964
Schad, Paulina S. 829
Schadendorf, D. 73, 267, 456
Schaefer, C. 914
Schaefer, N. 764
Schäfers, M. 943
Schäeler, N. 352
Scharath, N. 753
Schagh, D. 446
Schalk, E. 1041
Schaller, J. 506
Schambach, A. 629
Schanz, J. 1071, 1075, 1073
Schaper, T. 429
Schatz, S. 554
Schaub, V. 339
Schauberger, G. 764
Schauer, D. 912
Scheel, A. 810
Scheer, M. 912
Scheibenbogen, C. 159
Scheil-Bertram, S. 181
Scheiner, B. 425, 443
Schellenberger, B. 161
Schellhorn, H. 862
Schenk, J. 773
Schenk, M. 1002
Schenker, M. 436
Scheper, J. 512
Scherer, Laura-S. 426
Scherer, A. 983
Schetelig, J. 874
Scheuring, A. 1069
Scheuring, U. 218
Schichor, C. 847
Schick, B. 648
Schieferdecker, A. 976
Schiele, S. 92
Schierle, K. 689
Schieron, M. 724
Schiewer, V. 313, 705, 717, 743,
762, 844
Schildhaus, Hans-U. 276, 344, 507,
752, 792, 815
Schildmann, J. 198, 523, 799, 816, 1039
Schilling, G. 616
Schilling, J. 11, 80, 288
Schilling, O. 586
Schimanski, Carl C. 368
Schimmelpfennig, J. 621
Schimmöller, L. 852
Schindlbeck, C. 114
Schindler, C. 612
Schindler, H. 482
Schinke, T. 120
Schinköthe, T. 66, 870, 877, 899
Schirmer, M. 101, 34
Schirmer, Markus A. 78, 227, 713,
747, 757, 776, 584
Schjesvold, F. 150
Schlack, K. 253
Schlag, R. 869
Schlaiß, T. 656
Schlamann, M. 446
Schlampp, I. 36
Schlander, M. 415
Schlecht, S. 386
Schlecht, U. 902
Schleicher, Julia T. 426
Schlemmer, H. 852
Schlenska-Lange, A. 67, 211
Schlesinger-Raab, A. 311, 539
Schlesner, M. 669
Schliephake, H. 329, 566
Schlößer, Hans. A. 428, 502, 649
Schmalfeldt, B. 312
Schmall, A. 327
Schmautz, M. 708
Schmeling, B. 547
Schmid, I. 356
Schmid, Kurt W. 199, 276, 344, 416,
507, 518, 622, 752
Schmid, P.r 608
Schmidinger, M. 151
Schmidt, A. 870, 877, 899
Schmidt, D. 631
Schmidt, H. 198, 499
Schmidt, L. 197
Schmidt, M. 66, 340, 756
Schmidt, R. 689
Schmidt, S. 663
Schmidt, T. 1002
Schmidt, T. 169, 172
Schmidtmann, I. 368
Schmidt-Wolf, I. 635
Schmiedeknecht, A. 262
Schminke, B. 566
Schmitt, D. 78
Schmitt, J. 515, 523, 531, 799, 804, 1039
Schmitt, N. 12
Schmitt, T. 1041
Schmitz, J. 912
Schmitz, M. 445, 680
Schmoeckel, E. 132, 571, 118
Schmolling, J. 663
Schmutz, G. 429
Schmutz, M. 669
Schmutzler, Rita K. 361, 663, 44
Schnabel, A. 1023
Schnabel, M. 82
Schnaubelt, R. 522
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Oncol Res Treat 2022;45(suppl 1):7–284 Author Index280
Schneeweiss, A. 340, 1027, 1040, 676
Schneider, C. 642
Schneider, D. 673
Schneider, F. 522
Schneider, Marc A. 482, 707
Schneider, M. 1002
Schneidewind, L. 23
Schnell, K. 118
Schnell, O. 140
Schnell, R. 245
Schnelzer, A. 114
Schnitzler, P. 482
Schnöder, Tina. M. 323
Schochter, F. 340
Schoenfeld, Adam J. 690, 700
Schoenhacker-Alte, B. 1045
Schoer, O. 515, 523, 531, 799, 1039
Schöski, P. 486
Scholl, I. 312, 418, 626
Scholz, C. 171
Schömig-Markiefka, B. 810, 812
Schönburg, S. 198
Schönfelder, R. 780, 794, 795
Schönherr, C. 82
Schostak, M. 152, 326, 898
Schott, S. 569
Schrader, Andres J. 253
Schran, S. 428
Schrauder, Michael G. 269
Schröder, B. 288
Schröder, J. 103, 211, 280
Schröder, J. 780, 794, 795
Schröder, U. 262
Schröder, W. 810
Schrodi, S. 441, 114
Schub, N. 679
Schubert, J. 485
Schubert, K. 47, 244
Schubert-Fritschle, G. 311, 539, 114
Schuhmacher, L. 855
Schuler, Markus K. 702, 804, 486, 635
Schuler, M. 20, 276, 337, 344,
507, 518, 752, 792
Schuler, P. 131
Schuler, U. 134
Schüler, K. 751
Schüler-Toprak, Su. 347
Schulte, Johannes H. 201
Schultheis, A. 446
Schultheiss, M. 425
Schultz, A. 238
Schultze-Mosgau, S. 430
Schulz, C. 116, 911
Schulz, Hans-U. 801
Schulz, H. 137, 634
Schulz, L. 170
Schulz, M. 621
Schulze, M. 82
Schulze, S. 198, 200, 229
Schulz-Wendtland, R. 31
Schumacher, B. 276, 344, 752
Schumann, C. 265
Schündeln, M. 561
Schunn, F. 36, 191, 500
Schuster, A. 117
Schuster, J. 432
Schuster, S. 385
Schuster, Stephen J. 349
Schütt, P. 152
Schütte, K. 134, 635
Schütte, W. 33, 99
Schüttfort, Victor M. 972
Schütze, F. 385
Schütze, S. 662
Schwab, R. 451, 471, 473
Schwamborn, K. 272
Schwarz, N. 829
Schwarzenbach, C. 768
Schweiger-Eisbacher, C. 524
Schwenk, B. 1066
Schwentner, L. 656, 658
Schwinn, T. 996
Schwitter, M. 66
Scott, E. 991
Scriba, D. 694
Sebastian, M. 135, 280, 694,
1007, 1047
Sebens, S. 179, 209, 490, 1001
Seehausen, A. 642
Seemann, C. 179, 490
See-Zepeda, W. 287
Segeth, F. 929, 1024
Segmüller, T. 724
Sehn, Laurie H. 891
Sehouli, J. 159, 291, 302
Seibold, P. 970, 946
Seidel, N. 874
Seif, A. 292, 1069
Seif Amir Hosseini, A. 1077
Seifert, M. 40
Seifert, M. 799
Seiler, S. 1027
Seitz, S. 611, 903
Seiz, E. 143
Seliger, B. 128
Selle, F. 674
Semrau, S. 261, 476
Sender, A. 699
Sendler, A. 1007
Senft, C. 568
Senger, C. 847
Seraj, J. 1074
Seraphin, Tobias P. 716
Serrano, A. 410
Servant, N. 916
Seuerlein, T. 714
Seymour, John F. 411
Shadman, M. 374
Shah, M. 277
Shah, N. 709
Shah, Nirav N. 349, 516
Shah, R. 413, 482, 707
Shaheen, M. 157
Shahin, M. 674
Shao-Weng Tan, D. 255
Sharan, K. 950
Sharman, J. 166, 891
Shehu, E. 499
Shen, L. 1074
Sherman, E. 277
Shi, L. 337
Shi, L. 968
Shi, X. 16
Shimizu, C, 436
Shin, Ho-Jin 891
Shin, Sang W. 840
Shitara, K. 1074
Shore, N. 327, 328, 326
Shortt, J. 956
Shrestha, Y. 908, 911, 218
Siaplaouras, J. 673
Sibbertsen, F. 120
Sibille, A. 256
Sichward, Lara H. 507
Sicking, A. 380
Siebel, P. 293
Siebenbach, Hans U. 211
Siebert, S. 727, 735
Siebert, U. 947, 955, 1032, 1016
Siebolts, U. 853
Siefer, O. 446
Siegel, D. 534, 560, 208, 709
Siegert, A. 681
Siegle, A. 888
Sieglinde, P. 873
Siegmund, B. 855
Siegrist, M. 548
Siener, R. 852
Siepermann, M. 974, 575
Sieverding, M. 197
Sikic, D. 79
Silber, Y. 669
Silberg, M. 253
Silling, S. 446
Simanovich, E. 329
Šimkovič, M. 374, 414
Simon, R. 1053
Simons, E. 739
Simpson, D. 956
Simson, Barbara W. 92
Singal, Amit G. 32
Singer, S. 656, 658, 804
Sinn, M. 731, 735
Sinner, F. 425, 443
Sivaloganathan, S. 815
Siveke, J. 20, 344, 752, 792
Skarbnik, Alan P. 166
Škaro, A. 579
Skatkova, O. 906
Skikne, B. 287
Skof, Anna S. 764
Sladek, B. 1037
Slamon, D. 309
Sleeman, J. 388
Slomovitz, Brian M. 674
Smeets, R. 312
Smit, D. 120
Smit, H.J.M. 256
Smith, A. 308
Smith, J. 605
Smith, M. 328, 327, 326, 952
Snapir, A. 326
Soerensen, L. 760
Sohoni, S. 411
Sokol, Ethan S. 223
Solar, S. 1062
Solbach, C. 269, 504, 1027
Soldatenkova, V. 255, 277
Solomayer, Erich-F. 426
Solomon, B. 255
Solomon, S. 968, 967
Downloaded from http://karger.com/ort/article-pdf/45/Suppl. 3/6/4143722/000521004.pdf by guest on 05 March 2024
Oncol Res Treat 2022;45(suppl 1):7–284Author Index 281
Sommer, S. 669
Sommerlatte, S. 523, 816, 1039
Song, Yu Q. 891
Sookthai, D. 82, 85, 357
Soysal, Savas D. 104, 89
Spahic, E. 715
Spall, Thomas. 385
Spanier, G. 739
Späth-Schwalbe, E. 171
Speel, Ernst-J. 446
Speer, S. 261
Speiser, D. 397, 572, 722, 1061
Sperk, E. 970, 522, 946
Spiekermann, K. 1041
Spielmann, M. 1022
Spier, I. 379
Spitzner, M. 1
Spix, C. 934
Spohn, Simon K.B. 591
Sprecher, B. 899
Spring, L. 135
Springer, F. 5, 616, 1030
Srinivasan, S. 328
Sroczynski, G. 947, 955, 1032, 1016
Stadelmann-Nessler, C. 815
Stadtmauer, Edward A. 534
Staehler, M. 67, 222
Staemmler, H. 957
Stahl, M. 1074
Stahler, A. 260
Stähler, M. 128
Stahlhut, K. 167
Staib, F. 368
Staib, P. 152, 870
Stalf, H. 673
Stamm, N. 748
Stamm, P. 980
Stammann, C. 204
Stancato, Louis F. 201
Stange, D. 510
Stangenberg, M. 895
Stangl, Gabriele I. 499
Stangner, K. 381
Starbatty, B. 90
Statsenko, G. 908
Stäuber, A. 55
Stauch, M. 869
Stauch, T. 869
Stecher, M. 1014
Steckelberg, A. 499
Stecklum, M. 243
Steeb, T. 456
Steeghs, N. 1064
Steenbuck, Ines D. 586
Stefanjuk, S. 588
Steen, B. 486
Steens, J. 556
Stegen, G. 426
Steger, F. 111, 146
Stegger, L. 943
Stegmann, S. 198
Stehr, Antonia M. 864
Steidl, E. 567
Steifensand, F. 353
Stein, A. 357, 731, 1064, 486, 826
Stein, B. 720, 951
Stein, H. 40
Stein, T. 368
Stein, U. 524, 388, 605
Steinbach, Joachim P. 567
Steinborn, J. 416, 622
Steindorf, K. 197, 1040
Steinecke, M. 156
Steiner, T. 152
Steinestel, K. 959
Steinhagen-Thiessen, E. 159
Steinkasserer, L. 102
Steinmann, D. 547
Stelljes, M. 268
Stemmler, Marc P 864
Stenzinger, A. 413, 482, 707
Stenzl, A. 128, 881
Stepan, L. 967
Stephan, Lars U. 1049, 1052
Stephan-Falkenau, S. 518
Stephanou, M. 157
Sternberg, Cora N. 952
Steurer, S. 1031
Stewart, R. 911
Stickeler, E. 246, 269, 931
Stie, M. 1067
Stief, Christian-G. 359
Stiens, Ray Maria V. 507
Stilgenbauer, S. 349, 411
Stingl, J. 198
Stintzing, S. 103, 260, 563, 624,
1026, 1049, 1052
Stobart, H. 946
Stöckle, M. 128, 195, 556
Stoecklein, Nikolas H. 745
Stoetzer, Oliver J. 306
Stoian, R. 513
Stojadinovic, A. 337
Stoklossa, C. 159
Stöltzing, O. 963
Stolz, R. 547, 720, 951, 692
Stölzel, F. 874
Stölzel, F. 874
Stössel, S. 673
Stöter, O. 823
Stöver, I. 606, 433
Strack, M. 140, 460, 646
Strahl, A. 895
Strassburg, Christian P. 995, 921
Straßen, U. 272
Stratenwerth, B. 43, 53
Sträter, J. 1066
Straub, M. 735
Strauch, K. 996
Strauß, A. 153, 266
Strebhardt, K. 565, 580
Streckmann, F. 974, 136
Strehl, H. 42
Streitbürger, A. 450, 673
Strewinsky, N. 972
Ströbel, P. 292
Strohbücker, B. 90
Stromberger, C. 262
Stroosma, O. 119
Stroszczynski, C. 813
Strotmann, J. 814
Strueder, Daniel F. 228
Stuhlert, C. 426
Stummer, W. 943
Sturla, S. 53
Sturm, N. 425
Sturmheit, T. 933
Stürzl, M. 864
Stürzl, R. 355
Stuschke, M. 135
Stutz, R. 426
Stüwe, C. 47, 244
Suárez Rodríguez, C. 158, 222
Subbiah, V. 255, 277
Südho, T. 873
Sugg, J. 881
Sültmann, H. 482
Surmann, B. 961, 1056
Surovtsova, I. 177, 390, 392
Surrow, A. 1001
Süß, C. 111, 146
Sütterlin, M. 522
Suzuki, H. 952
Suzuki, K. 971
Swart, E. 934
Symank, J. 512
Symonds, R Paul 946
Szarvas, T. 507
Szymczak, S. 255
T
Tabatabai, G. 254, 758
Tabernero, J. 1044, 1074
Tahmasbi Rad, M. 580
Tak, Paul P. 758
Takezako, N. 971
Talalaev, N. 705
Talaulicar, R. 1073
Talbot, Christopher J 946, 970
Tam, Constantine S. 374, 349
Tamaskovics, B. 262, 476, 63
Tamborero, D. 916
Tammela, Teuvo L.J. 326, 952
Tammer, I. 809
Tan, P. 956
Tan, X. 516
Tang, D. 281, 282
Tannapfel, A. 523, 788, 1039
Tannert, A. 323
Tat Ling, M. 956
Tatsch, L. 768
Taube, C. 518
Taubert, H. 233
Tauscher, M. 621
Tavenrath, S. 844
Teichert-von Lüttichau, I. 356
Telzerow, E. 359
Templin, M. 325
Tenschert, E. 576
Terhaag, J. 66
Terheyden, P. 544
Terjung, I. 912
Tesch, F. 799
Teschendorf, C. 523
Teschner, A. 86
Teschner, D. 1041
Testa, L. 436
Teufel, A. 10
Tewes, M. 20, 562
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Oncol Res Treat 2022;45(suppl 1):7–284 Author Index282
Teynor, A. 180
Thelen, M. 428, 502, 649
Theodoraki, Marie-N. 131
Theoklitou, D. 570
Thiele, S. 952
Thielert, M. 929
Thiemann, E. 269
Thieme, R. 399, 685, 689,
697, 643
Thill, M. 246, 269
Thimme, R. 211, 714
Thol, F. 287
Thomaidou, D. 151
Thomas, J. 131
Thomas, M. 16, 47, 135, 244,
280, 370, 413, 482,
707, 840, 888, 1062
Thomas, S. 275
Thompson, J. 73
Thomsen, Andreas R. 646
Thomssen, C. 751
Thong, M. 532, 358
Thronicke, A. 299, 497, 964
Thul, I. 426
Thuss-Patience, P. 976
Thy, S. 149
Tiede, A. 1022, 975
Tiemann, M. 554
Tietl, J. 200
Tilki, D. 972
Tiller, U.e 568
Tilly, H. 891
Timmermann, B. 450
Timotheou, A. 921
Timrott, K. 601
Ting, S. 344, 507, 752
Tinker, A. 730, 1055
Tirier, S. 737
Todenhöfer, T. 328, 952
Tolaney, S. 936
Toma, M. 921
Tomanek, A. 647
Tomasini, P. 255
Tombal, B. 952
Tometten, L. 1014
Tometten, M. 739
Tomicic, M. 768
Tonk, Christian H. 870, 877, 899
Tonn, Jörg-C. 847, 613
Tonndorf-Martini, E. 47, 244
Topaly, J. 239
Topf, C. 626
Topp, M. 339
Tortora, G. 950
Tothill, Richard W. 223
Touchefeu, Y. 714
Towhidi, T. 1042
Tozzi, A. 640
Traubeck, S. 728
Traxdorf, M. 261
Trebicka, J. 761
Treeck, O. 347
Treese, C. 855
Treiber, H. 465
Tremmel, A. 1065
Trepel, M. 669
Treppner, S. 540
Trillsch, F. 118, 132, 537, 571
Tripal, P. 864
Trněný, M. 891
Trocchi, P. 934
Trojan, J. 443
Trostdorf, K. 171
Trunova, N. 868
Truppel-Hartmann, A. 560, 709, 208
Tschmelitsch, J. 867
Tsiouris, A. 197, 1057
Tsuboi, M. 50
Tubío-Santamaría, N. 323
Tüchler, A. 44
Tufman, A. 728, 989, 1047
Tully, K. 79
Tunn, P.-U. 410
Turnbull, C. 906, 916
Turner, N. 283
Tuschy, B. 522
Tusquets, I. 674
U
Ubels, J. 415
Uacker, L. 900
Ugidos, M. 287
Ugocsai, P. 903
Ugurel, S. 267
Uhl, N. 1059
Uhl, W. 523, 814, 788
Uhlenbruch, Y. 450
Uhlig, J. 211
Ulbricht, H. 874
Ulbricht, S. 228
Uleer, C. 751
Uller, W. 813
Ullrich, A. 634
Ullrich, R. 690, 700
Ulys, A. 326
Ungar, N. 197
Ungelenk, M. 323
Unger, C. 229
Unger, S. 307
Unsöld, L. 888
Untch, M. 504, 1027
Urban, L. 920
Urbschat, I. 354
Ursol, G. 16, 33
Usenko, G. 414
Utikal, J. 73, 267
Uttinger, K. 396
Uxa, S. 381
V
Valdagni, R. 946
Valenta, S. 180
Valentini, J. 720, 951
Vallieres, E. 33
van Boemmel, F. 425
Van Cutsem, E. 950, 1044
van de Donk, Niels W.C.J. 534
Van den Bosch, V. 119
Van den Eertwegh, A. 151
van Oorschot, B. 1062
van Troostenburg, A. 252
Vasiliev, A. 16
VAsiljeva, K. 346, 294, 351
Vattai, A. 828
Vcev, A. 579, 760
Vecchione, L. 260, 563, 1026
Vega, A. 970, 946
Vehreschild, Jörg J. 1014, 1041
Vehreschild, M. 1041
Velarde, Luis Enrique C. 868
Velcheti, V. 989
Veldeman, L. 970, 946
Veltrup, E. 94
Veltzke-Schlieker, W. 855
Veneris, J. 730, 990, 1055
Venerito, M. 59, 425, 443
Venkataramani, V. 1008
Verholen, F. 327
Verret, W. 32
Verzoni, E. 151
Veselinovic, K. 1059
Vetter, M. 751
Viale, G. 210
Viestenz, A. 853
Viezens, L. 895
Villalobos-Bollen, M. 888
Virchow, I. 276, 344, 507, 752, 867
Vjaters, E. 326, 328, 327
Vogel, A. 103, 990
Vogel, P. 150, 691
Vogel, T. 390
Vogelhuber, M. 339
Vogl, I. 902
Vogt, T. 648
Voigt, M. 934
Voigtländer, S. 618
Voiss, P. 547, 692
Voit, F. 1014
Voitko, O. 908
Voland, A. 614, 617, 741
Volk, A. 663
Völkl, S. 31
Volkmer, Anne K. 785
Vollkommer, T. 312
Vollmann-Zwerenz, A. 613
Voltz, R. 634
vom Endt, C. 884
von Amsberg, G. 972
von Baumgarten, L. 537, 555
von Bergwelt-Baildon, M. 428, 502, 537,
649, 1041
von Brandenstein, M. 661, 698, 701,
708, 711, 715
von Bubno, N. 603, 1042
von der Assen, A. 522
von der Brelie, C. 465
von der Grün, J. 476, 63
von der Heyde, E. 67, 63, 266, 869, 103
von Havranek, M. 134
von Krosigk, V. 385
von Levetzow, C. 912
von Lilienfeld-Toal, M. 1014, 1041
von Meyenn, M. 906, 916
von Moos, R. 73
von Suchdoletz, H. 1007
von Trott, P. 497
von Witzleben, A. 131
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Oncol Res Treat 2022;45(suppl 1):7–284Author Index 283
Vordermark, D. 474, 499
Vorwergk, J. 662
Vosbeck, J. 89
Voß-Böhme, A. 639
Vucinic, V. 5
Vucinic, V. 610
Vulsteke, C. 674
Vynnychenko, I. 33
Vynnytska-Myronovska, B. 195
W
Wabinga, H. 823
Wach, M. 414
Wach, S. 233
Wachter, A. 815
Wacker, F. 852
Waddell, T. 158
Wagenpfeil, G. 426
Wagner, Anna D. 103
Wagner, Anne-C. 648
Wagner, D. 411
Wagner, D. 812
Wagner, J. 712
Wagner, Johannes M. 251
Wagner, Sa. 535
Wagner, S. 715
Wagner, S. 446
Wahib, R. 933
Wahlen, S. 914
Waidmann, O. 425, 443
Wainberg, Z. 1044
Wakelee, H. 33
Walawgo, T. 519
Waldenberger, D. 265
Waldenberger, D. 63
Walding, A. 50
Waldmann, A. 532
Walker, G. 210
Walker, P. 166
Waller, C. 1007
Wallis, M. 419
Wallwiener, D. 676
Wallwiener, M. 851
Walter, J. 568
Walter, J. 275
Walter, Robert Fred H. 416
Walter, S. 453
Walther, W. 201, 404, 524, 605
Walz, T. 659
Wang, G. 864
Wang, J. 151
Wang, J. 560, 208
Wang, Michael L. 516
Wang, Min H. 166, 414
Wang, P. 636
Wappenschmidt, B. 361
Ward, T. 970, 946
Warfsmann, J. 380
Warwas, Karsten M. 86
Waszak, A. 989
Watolla, M. 380
Webb, A. 970, 946
Weber, C. 456
Weber, F. 347
Weber, F. 604
Weber, Jan-P. 912
Weber, K. 761
Weber, M. 458, 493, 739
Weber, V. 862
Weberpals, J. 916
Wedding, U. 1039
Wedeken, L. 325, 524, 678, 718
Weder, W. 50
Wedig, T. 829
Wegener, N. 1023
Weger, K. 604
Weg-Remers, S. 415
Wegwitz, F. 588
Wehler, T. 370
Wei, Andrew H. 956, 287
Wei, R. 436
Weichenthal, M. 267
Weichert, W. 280, 114
Weide, R. 936
Weigel, M. 269
Weigert, E. 751
Weigmann-Faßbender, S. 874
Weiler, D. 277
Weiler, M. 1040
Weiler, N. 456
Weinke, M. 79
Weinkove, R. 374
Weirda, William G. 349
Weis, I. 851
Weisel, K. 150, 691, 709
Weiskirchen, R. 931
Weiss, C. 10, 522
Weiß, D. 586
Weißbach, J. 403
Weißbach, L. 204
Weitz, J. 787
Welker, L. 895
Wellesen, A. 134
Wellner, U. 1009
Welslau, M. 867, 869, 103, 63,
239, 612, 898, 414
Welt, A. 246
Wendler, O. 432
Wendling, J. 752
Wennhold, K. 428
Wensing, M. 204
Wenz, F. 522
Wenzel, C. 510
Wenzel, Gentiana I. 648
Werbrouck, P. 327
Werle, L. 1069, 1075, 866
Wermke, M. 370, 510, 690, 700
Werner, J. 219
Werner, T. 586
Werry, Jan-E. 458
Wesseler, C. 280
Wessels, S. 413
Wessolly, M. 199, 416, 518, 622
West, Catharine ML 946, 970
Westbrook, K. 309
Westphalen, B. 223, 537, 555, 779
Weth, J. 485
Wetzel, N. 67, 245, 259
Wetzig, S. 157
Weydandt, L. 190
Weykamp, F. 578
Whipple Neibauer, M. 337
White, D. 150
Whitston, D. 911
Wichmann, D. 593
Wichmann, G. 262
Wichmann, Y. 689
Wick, W. 1008
Wiedenmann, B. 855
Wiedenmann, N. 513
Wieditz, J. 1062
Wiegand, J. 266
Wiegand, S. 262
Wiegering, A. 396
Wiek, C. 561
Wieland, T. 902
Wieland, U. 446
Wienands, J. 1
Wienands, L. 180
Wiener, A. 673
Wiesweg, M. 276, 344, 518, 752
Wild, M. 828
Wild, Philipp S. 997
Wilde, F. 959
Wilhelm, M. 721, 506
Wilhelm, M. 40
Wilhelm, M. 177
Wilke, J. 280
Will, R. 749
Willborn, K. 694, 712
Wille, K. 1014
Willich, Stefan N. 159
Willimsky, G. 681
Willy, C. 869
Wilms, G. 204
Wiltink, J. 996, 1057
Wimberger, P. 291, 302, 676
Winde, G. 170
Winder, T. 103
Windisch, P. 360
Winer, E. 309
Winkler, Eva C. 961, 1056, 415
Winkler, F. 1008
Winkler, M. 547, 692
Winnand, P. 739
Winquist, E. 308
Winter, H. 482
Winter, M. 1064
Winzler, Cl. 392
Wirsik, N. 1002
Wirth, L. 277
Wirth, M. 152
Wirtz, R. 79, 94
Wirtz, S. 761
Wiskemann, J. 614, 617, 630, 673,
741, 1040, 321, 197
Wisser, S. 523
Wißmann, N. 1008
Witkowski, L. 788
Witt, C. 547
Witt, O. 749, 628
Witte, D. 788
Wittekindt, C. 446
Witteler, R. 302
Wittke, K. 159
Wittke, T. 673
Witzel, I. 312
Wlochowitz, D. 815
Wöckel, A. 246, 656, 658
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Oncol Res Treat 2022;45(suppl 1):7–284 Author Index284
Wodlej, C. 404
Wohlschlaeger, J. 416, 518, 622
Woldai, S. 889
Wolf, C. 100
Wolf, J. 255, 510, 912
Wolf, T. 259
Wolfarth, B. 159, 791
Wölfel, T. 410
Wolfer, S. 566
Wol, A.r 815
Wol, M. 874
Wol, T. 239, 867
Wömpner, C. 912
Wong, A. 553
Wong, S. 308
Woopen, H. 159
Wördeho, H. 74
Wörmann, B. 1039
Wörmann, C. 426
Wortmann, A. 82
Wöstemeier, A. 1035
Woyach, Jennifer A. 349, 166, 516
Wright, Gail. S. 636
Wright, J. 277
Wrobel, D. 66
Wu, K. 374
Wu, Yi-L. 840
Wuerein, D. 94
Wulf-Goldenberg, A. 243
Wullich, B. 79, 233
Wunderlich, H. 556
Würdemann, N. 446
Wurm-Kuczera, R. 467
Würstlein, R. 49, 298, 537,
555, 877
Wüstefeld, H. 964
X
Xie, M. 908, 911
Xu, Q. 12
Y
Y. Locker, G. 950
Yachnin, J. 690, 700
Yakoub-Agha, I. 709
Yang, Cheng-Ta 16
yang, c. 685
Yang, James Chih-H. 840
Yang, L. 380, 590, 740, 745
Yao, D. 971
Yao, R. 260, 563
Yatabe, Y. 50
Ye, D. 952
Yecies, J. 374
Yesilyurt, Umut U. 1001
Yew Fong, C. 956
Yildirim, A. 328
Yılmaz-Aslan, Y. 835, 1068
Ying Tan, S. 956
Yordanova, K. 648
Yu, H. 219
Yu, T. 166, 414
Yu, T. 608
Yushak, Melinda L 690, 700
Z
Zaccagnino, A. 195
Zacharias, S. 280
Zahn, Mark-O. 246, 82, 135
Zaiss, M. 246, 66
Zaman, K. 66
Zamboglou, C.os 591
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